In Book I Oliver Sacks describes his visit to Pingelap and Pohnpei in the Caroline Islands (now a part of the Federated States of Micronesia). On Pingelap (population 700) 5-10% of the people are completely colorblind; i.e. they have a rare hereditary condition called achromatopsia in which the retina has no functional cone cells. Rod cells, which normally provide peripheral and night vision, are their only source of vision. While partial colorblindness is common, achromatopsia is normally very rare. Sacks and Knut Nordby, a Norwegian scientist who is himself achromatopic, examined dozens of achromatopes on Pingelap and in a village of Pingelapese people on the larger Pohnpei.

In Book II Sacks takes the reader to Guam where he investigates (with his friend John Steele, a neurologist who lives on the island) the neurological disease called "lytico-bodig." The "lytico" form of this disease is a progressive paralysis similar to amyotropic lateral sclerosis, while the "bodig" form resembles parkinsonism. Both appeared in Guam after the Second World Way and now seem to be dying out. However, no one has ever determined their cause.

Sacks tells the story of his visit, while also discussing various hypotheses that have been considered and discarded over forty years of study. The last section of the book describes a trip to Rota, a small island north of Guam, where Sacks visits a forest of cycad trees and discusses his life-long fascination with these primitive plants.