In an 18 hospital study, 205 patients hospitalized with a diagnosis of manic-depressive illness, manic type, were treated upon discharge with lithium carbonate or placebo for a two-year period. Lithium carbonate was significantly more effective than placebo in preventing relapses (ie, affective episodes severe enough to require hospitalization or use of nonstudy drugs). The difference in treatment outcome between lithium carbonate and placebo was due mainly to the lower incidence of manic relapses on lithium carbonate. Patients on lithium carbonate also had a lower incidence of depressive relapses than patients on placebo but the limited incidence of severe depression in this sample makes it difficult to draw any conclusions regarding the prophylactic efficacy of lithium carbonate in depressive illness. The results from this trial coupled with those from other studies indicate that lithium carbonate combined with regular clinical appraisals is a safe and effective treatment for preventing relapse in manic-depressive illness.