Cole defined Macro Life as "life squared per cell", ie "Macro Life is to man what man is to the cell". Zebrowski, in the novel, regards Macrolife as an open-ended, expansive union of organic, cybernetic and machine intelligences (human and alien) with spacefaring as its means of dissemination.
The novel is split into three main sections.
(I) Sunspace: 2021 ... The Bulero family/corporation, inventors and marketers of Bulerite which is used to build the huge cities which house the Earth's (and colonies) teeming millions, are at the pinnacle of their influence and wealth. Unfortunately, it is discovered - too late - that the substance is inherently flawed, in that after a time it destabilizes and self-destructs with spectacular results. Gradually, all the Bulerite on Earth, and that on and in the space colonies throughout the solar system becomes unstable, causing destruction and megadeath.
The Bulero family manages to escape to Asterome, an orbiting colony situated inside a hollowed-out asteroid at the Moon's L5 point. Eventually, a means of providing Asterome with propulsion is discovered - necessary, as it becomes clear that there is so much Bulerite on Earth it is creating an expanding field of energy that could encompass the entire inner system. Asterome finally manages to leave the solar system, heading for Alpha Centauri, the nearest star.
(II) Macrolife: 3000 ... A thousand years later, Asterome has grown by adding concentric layers of shells around itself, and is now host to millions of humans and Humanity II cybernetic organisms.
The invention of engines that can surpass the speed of light has made it possible for the colony to explore far and wide; the second part finds them studying a planet orbiting the star Praesepe over 500 light years away. John Bulero, a young clone of one of the original Bulero's, decides to see what life is like on a planet, and lives for a while amongst the natives, descendants of a human colony that has reverted back to savagery. His experiences, while tragic, enable him to grow as an individual.
Eventually, Asterome travels back to the solar system to see how events there have unfolded. Their arrival coincides with the first time humans meet an intelligent alien species which is itself experimenting with Macrolife, and, together, the species begin a process of intermingling and further expansion into the universe.
(III) The Dream of Time ... A hundred billion years have passed, and Macrolife is now the dominant culture throughout the universe, which is, at this stage, beginning to contract into its final death throes. Most life is in the form of a Hyperpersonal Aggregate; an amalgam of individuals of all kinds. The aggregate re-individualizes John Bulero again, to help them solve the problem of how Macrolife can survive beyond the death of the Universe. Eventually, they discover many Macrolife survivors from many previous cycles of the universe, who help them to conquer time itself.