Working in a psychiatrically innovative environment created by the Government of Saskatchewan, Canada, Abram Hoffer and Humphry F. Osmond enunciated the adrenochrome hypothesis for the biogenesis of schizophrenia in 1952, slightly later proposing and, apparently, demonstrating, in a double-blind study, that the symptoms of the illness could be reversed by administering large doses of niacin. After placing the hypothesis within its ideological framework, the author describes its emergence and elaboration and discusses the empirical evidence brought against it. Hoffer's idiosyncratic diagnostic procedures, especially his creation and use of a supposed biochemical marker for schizophrenia, are examined. The author argues that Hoffer's conceptualization of schizophrenia, as well as his treatment approach, depended on a tautology. Following David Healy, the author treats the adrenochrome hypothesis as a version of a transmethylation theory, thus incorporating it into mainstream psychopharmacology.