Fixed daily doses of 20 mg, 40 mg, or 60 mg of fluoxetine, a highly specific serotonin reuptake inhibitor, were given to 84 depressed outpatients in a double-blind, placebo-controlled, randomized 6-week trial. The 20-mg dose produced improvement of depression in the moderate-severe depression group as expressed in significant reductions of scores on the Hamilton Rating Scale for Depression (p greater than or equal to .007) and the Patient Global Impressions scale (p greater than or equal to .011), and the 20-mg dose caused fewer side effects than did the higher doses. A mildly depressed group of patients showed no improvement at any dose level of fluoxetine.