Natural killer (NK) activity of human peripheral blood lymphocytes (HPBL) was studied in 32 alcoholics and 15 control subjects in a 4-h chromium release assay using K562 tumor target cells. The natural killer activity of human peripheral blood lymphocytes in alcoholics was significantly higher than the level found in the control group. NK activity of PBL from alcoholics was still higher than that of similarly treated PBL from control subjects after carbonyl iron and magnet treatment, or after passage through a nylon wool column or after removal of cells rosetting with sheep erythrocytes. Changes in T cell, B cell or macrophage populations, therefore, are not the mechanism for increased NK activity in alcoholics.