Moderate to severe papulopustular acne requires systemic and long-term treatment, the first choice therapy most often being tetracycline. In this double-blind randomized parallel-group study a new erythromycin derivative, erythromycin acistrate (EA), a 2′-acetyl ester prodrug of erythromycin, was compared with routine tetracycline treatment. The study group comprised 60 patients with moderate or severe acne who were treated for up to 6 months. One patient in each treatment group was completely cured within the first 3 months. After 6 months' treatment a further patient in the tetracycline group was completely cured. There were no significant changes in laboratory test values. Both drugs were well tolerated: one patient in each treatment group discontinued treatment due to diarrhoea during the first week. EA is a safe and well-tolerated alternative to tetracycline for the systemic treatment of acne.