This brief compilation of some of the NIMH studies of manic-depressive and depressed patients suggests several conclusions: (1) A phenomenological approach to the affective disorders employing reliable behavioral and biological measurements can reveal and permit documentation of some basic aspects of these disorders; for example, the sequential psychological and biological changes which occur as part of the ‘switch process’ between different affective states. (2) The use of drugs with well-studied biochemical effects permits controlled manipulation of biochemical and behavioral events and can strengthen or clarify hypotheses based upon indirect evidence. For example, the studies with T-dopa and α-methyl-p-tyrosine seem to confirm other data suggesting the importance of catecholamines, especially dopamine, in mania. Simultaneously, these studies with these drugs suggest that depression may prove to be a more complex and difficult-to-study problem, with current hypotheses apparently representing an oversimplified view. (3) The importance of mania as a distinguishing characteristic of the bipolar patient group was affirmed by clinical, psychological, biochemical, and pharmacological findings. It is hoped that the data presented and hypotheses suggested will stimulate future research and will contribute to the psychological and molecular understanding of these serious disorders.