By random happenstance, Stoat incurs the wrath of Twilly Spree, an eccentric millionaire, when he dumps rubbish out of his car window onto the highway. Spree obsessively pursues a path of retribution for littering, tracking Stoat back to his Fort Lauderdale residence and later breaking into the home where he and his wife Desirata live to find information about him.
There Spree is shocked to find that Stoat has a wall full of animal trophies, all from canned hunts in Florida. He removes their glass eyes and arranges them in a pentagram form on Stoat's desk; later Stoat's Labrador, Boodle, swallows some of the glass eyes, which makes him the "sick puppy" of the novel's title.
Then Spree rents a truck full of garbage and dumps the whole smelly truckload on Desirata Stoat's BMW convertible, which is parked, with its top down, in the parking lot of a restaurant. Some time later Stoat finds his own car full of dung beetles (which he mistakes for cockroaches). Stoat does not connect these acts of vandalism to his littering, and does not change his ways, but declares that the world itself is sick. Eventually, his Labrador is abducted.
When Desirata meets Spree to get the dog back, two unforeseen things happen: Spree learns all about the Shearwater Project, which he of course vehemently opposes; and he and Desirata fall in love with each other. She converts to Spree's cause and, as a condition for the return of the dog, persuades Stoat to have governor Artemus stop the Shearwater Project by vetoing the bridge which would be required to enable development.
Clapley faces angry questions from his backers following the veto of the project. Both he and Stoat come to the conclusion that it is necessary to get hold of the crazy extortionist, who has sent the ear and the paw of a dead black Labrador that he found on the highway to Stoat to make it absolutely clear how serious he is. Clapley assigns a contract killer that he has on retainer, Gash, to find and get rid of Spree.
Stoat, in an effort to avoid the Shearwater Project being tainted with violent death, seeks out and locates ex-governor Clinton Tyree, who vanished about 20 years ago after a short and unsuccessful (but honest) term of office and is said to be hiding out somewhere in the remaining wilderness of Florida. Artemus knows the only way to blackmail Clinton Tyree: Clinton's mentally disturbed brother Doyle is still on the governor's payroll as the keeper of a lighthouse that has not been in use for years. Artemus advises Tyree that his brother will be tossed out on the street if he doesn't locate Spree.
Meanwhile Spree and Desirata, and the dog, whom Spree names McGuinn, have become an item. In an absurd interlude, the couple while away a pleasant day visiting and talking with Spree's mother, with Palmer Stoat gagged, blindfolded and tied to a rocking chair next to them.
Both Gash and Clinton Tyree eventually turn up on Toad Island. Gash is the first to arrive, and he succeeds in overwhelming Twilly and Desirata. He shoots Twilly, leaving him lying in a pool of blood on the ground outside their car, and is just about to rape Desirata when he is playfully attacked by McGuinn, who jumps on his back and humps him, and won't let go of him. Gash does not manage to rape Desirata because he can't get an erection with the big dog on his back.
Clinton Tyree then appears on the scene: He shoots Gash twice, first in the knee and then through the mouth, severing his tongue. Finally he drags him to the construction equipment and parks one of the bulldozers on Gash's legs and leaves him dying there. By means of a mobile phone they others call a helicopter. Twilly and Desirata are rescued, and Twilly Spree is hospitalized.
Gash manages to get a cell phone out of his pocket, but without his tongue, his words are misunderstood,and 911 switches him to a Spanish-speaking operator who can't understand him either.
Spree recovers from his gunshot wound and joins Clinton Tyree for a final attack on the land developers, politicians and lobbyists. Spree and Tyree have been tipped off about an informal meeting at the Wilderness Veldt Plantation where Artemus, Clapley, Stoat and Willie Vasquez-Washington, the corrupt chairman of the House Appropriations Committee, want to fix a deal that would eventually greenlight the Shearwater Project. Clapley has been promised by Stoat that he can shoot a "killer rhino" and keep its horn as an aphrodisiac. Spree and Tyree, with McGuinn in tow, are there too, watching from the hill, but have no real plan. The dog yanks his leash free, runs down to the shooting party, and attacks the "killer rhino"—actually a very old, dying animal. When it is attacked by the harmless McGuinn, however, the rhino jumps up and starts running around. Clapley and Stoat attempt to shoot the animal, but accidentally shoot at each other. Clapley is picked up by the rhinoceros and carried around on its horn, while Stoat is stomped to death.
The governor and Vesquez-Washington retreat, and since Vasquez-Washington filmed everything in color, the governor quickly offers him anything that he wants to not release the film.
Only a few people show up at Palmer Stoat's funeral. Meanwhile, Twilly Spree and Clinton Tyree are driving along the highway towards Tyree's wilderness when they see another group of litterbugs throwing lighted cigarette butts, empty bottles and other rubbish out of their speeding car and onto the dry grass near the shoulder of the road. They immediately agree the they have to teach them a lesson.
- "Now you have land use attorneys whose job it is to get around master plans and zoning restrictions, and they make good livings off finding loopholes or making loopholes so people can build something where they weren't intended to build it," he says. "A good example is Key West. . . . They live off the Hemingway mystique, they trade on the Hemingway mystique, constantly. If Hemingway were alive, he'd take a flame-thrower to Duval Street, and that's the truth. Fifty T-shirt shops? Give me a break."
- "Hiaasen is best known for serving up heaping helpings of just desserts [sic]. His bad guys are the baddest, and his good guys are anything but the Dudley Dorights of popular fiction. How does Hiaasen come up with his new means of doling out justice to the terminally greedy? Just when you think, "they'll never get out of this mess," he devises a plan, and they're off and running."
Some reviews may suggest that the novel is not appreciated.
However this same review goes on to explain...
- "Sick Puppy is ultimately as unforgiving as nature's order. The characters are not likeable. There is no redemption or apology."
- "But that's Hiaasen's design. In the end, we are treated to one of his favorite devices, the epilogue with thumbnail descriptions of the fates of many of his characters. Some of the scoundrels prosper, some don't. There's the sense that there is more work to be done. Sure, Hiaasen himself may not be ready to kidnap the dogs of unregenerate litterbugs or clobber drunken jet skiers, but it's the thought that counts."