The possibility of a prophylactic action of lithium in recurrent affective illness has been a subject of significant controversy, perhaps because of some valid methodological critiques and also because we are dealing with a relatively new possibility, that of prophylactic chemotherapy. In the history of science, new technologies have had profound impact on theory and research methods. This is especially true in medicine, where new treatments often have far-ranging effects on theoretical concepts, as well as important consequences for the diagnosis and treatment of patients. Within psychiatry, such changes are currently occurring in the treatment of the affective disorders. The therapeutic activity of lithium in this context has been of profound significance in investigating issues of symptomatology, diagnosis, and prognosis of these disorders, as have studies of the pharmacology and modes of action of psychotropic drugs found effective in affective disorders. Now, quite apart from the still-debated issue of the therapeutic efficacy of lithium for an acute manic episode, we must here direct our attention to the even more hotly debated issue of the prophylactic activity of lithium against recurrences of both manic and depressive episodes. If the reports that indicate such prophylactic effects should be fully corroborated, then we will have reached an important ear, one wherein the idealized goal of prevention of episodes of mental illness can, for the first time in psychiatry, realistically be entertained. Before we look at the data on prophylaxis, we should briefly restate the consensus regarding the action of lithium on a current manic or depressive episode. In regard to mania, a conclusion based on the available literature (not unanimous, but accepted) is that lithium is superior to placebo. When compared to other effective antipsychotic agents, the consensus is that in general it might be equivalent to chlorpromazine or haloperidol in regard to outcome, but not in regard to speed of action. With depression, the situation is much less clear. The open studies, even by weight of numbers, imply no clear efficacy. The most recent controlled study, by Mendels et al., 1 compared lithium and desipramine in a total of 24 patients and found the drugs equipotent. However, a significant critical issue was the absence of a placebo group for comparative purposes.