We assessed the efficacy of lithium carbonate in the treatment of 457 male alcoholics in a double-blind, placebo-controlled Department of Veterans Affairs Cooperative Study. Alcoholics either without depression or with a history of major depression, current major depression, or dysthymic disorder were studied. Two hundred eighty-six alcoholics without depression and 171 alcoholics with depression began the 52-week outpatient study; 172 alcoholics (60.1%) without depression and 108 alcoholics (63.2%) with depression completed the study. Among both all alcoholics who began the study and a subgroup who completed the study, no significant differences between alcoholics who took lithium and those who took placebo were found for the following outcome measures:number of alcoholics abstinent, number of days of drinking, number of alcohol-related hospitalizations, changes in rating of severity of alcoholism, and change in severity of depression. Similarly, no significant differences were found when only the 82 alcoholics compliant in taking lithium and the 89 alcoholics compliant in taking placebo were considered. In our study, lithium treatment did not affect the course of alcoholism in either depressed or nondepressed alcoholics.