Retrospective studies have suggested that D-penicillamine (DPA) in conventional high dosages (750-1000 mg/d) may be efficacious in treating the skin and visceral complications of systemic sclerosis (SSc), particularly when used early in the disease. The course of skin thickening and the occurrence of renal crisis and of death were examined in a recent randomized controlled 2-year trial of high- dosage DPA (750-1000 mg/d) versus low-dose DPA (125 mg every other day). Skin thickening improved in both groups to a similar extent, and the occurrence of renal crisis and of death were not different in the two groups. Although the trial was not designed to answer the question of whether low-dosage DPA is effective, it did suggest that there is no advantage to using DPA in doses higher than 125 mg every other day.