In a retrospective study on progressive systemic sclerosis, we compared 73 patients who had received D-penicillamine therapy for a minimum of 6 consecutive months with 45 patients who had not received this drug. All patients had diffuse sclerodermatous skin changes and early disease (less than 3-years duration). D-Penicillamine was prescribed for an average of 24 months (range, 6 to 68 months) with a maximum daily dose of 500 to 1500 mg (median, 750 mg). During a mean follow-up interval of 38 months, the degree and extent of skin thickness, determined on physical examination, decreased considerably more in the patients treated with D-penicillamine than in patients in the comparison group (p = 0.07). The rate of new visceral organ involvement was reduced in patients treated with D-penicillamine, especially for the kidney (p = 0.01). Patients treated with D-penicillamine had a greater 5-year cumulative survival rate (88% versus 66%, p less than 0.05). Therapy with colchicine (23 patients) or immunosuppressive agents (26 patients) was not associated with these improvements.