A multicenter randomized 4-week interindividual double-blind study was carried out in 58 hospitalized patients with major depressive disorder (DSM III 296.23,296.22,296.33,296.32,296.53 and 296.52) to test the dose-effect relationship of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram: 3 × 0.25 mg, 3 × 0.50 mg and 3 × 1.00 mg rolipram/day. With respect to the desired effect, the 3 × 0.50 mg dosage stood out from the others in almost all relevant parameters. With respect to the response rate, the efficacy of the 3 × 0.25 mg dosage was about the same as that reported in the literature for placebo. The inferior performance of the 3 × 1.00 mg dosage compared to the 3 × 0.50 mg dosage might indicate a reverse U-shaped dose-effect relationship. There was good tolerance to all three dosages. There were no findings that might cast doubt on the safety of the dosages