The efficacy of lithium carbonate as a treatment for manic-depressive illness has stimulated a reevaluation of the syndrome. In this paper, the authors review the obstacles to timely diagnosis of manic-depressive illness in the adolescent. Three cases are presented demonstrating the usefulness of a unitary concept in which manic-depressive illness is understood and appreciated as having a physiologic basis, manifesting its effects in the total body system. The heterofore diverse and confusing psychological and behavioral symptoms of manic depressive illness in adolescents become intelligible when regarded as secondary phenomena: the psychic experience of the process as filtered through the psychological constitution of the individual adolescent.