Findings from the first prophylactic study of a much larger project begun in 1968 by the Veterans Administration and the National Institute of Mental Health are reported. Patients from twelve Veterans Administration Hospitals and six public or private hospitals were followed for two years. All two hundred and five patients had been hospitalized with the diagnosis of manic-depressive illness, manic type. Lithium carbonate, at serum levels between 0.5 and 1.4 mEq./liter, was significantly more effective than placebo in preventing relapses. Relapse was defined as an affective disorder severe enough to require hospitalization or the use of a nonstudy drug. Because of the low incidence of depressive episodes, the data could not support the assertion that lithium carbonate is prophylactic against depressive relapses.