Numerous drugs have been recommended for the treatment of systemic sclerosis, but without any significant effect on the fibrotic stage of this disorder. Because recombinant gamma-interferon (gamma-IFN) is a potent and selective inhibitor of fibroblast proliferation and collagen production by human dermal fibroblasts in vitro, we assessed the effects of gamma-IFN treatment on the skin and on pulmonary function in patients with systemic sclerosis. Fourteen patients entered the study, and nine completed the 12-month trial. Fifty micrograms/day of gamma-IFN was administered subcutaneously 3 days per week. At the end of the 12-month treatment period a significant improvement was observed in total skin score, and blood gas analysis showed a significant increase in Pa O2 during therapy with gamma-interferon. Other clinical parameters (dysphagia, Raynaud's phenomenon, cardiac involvement) were not altered significantly. No serious adverse effects were noted. These results suggest a beneficial effect of gamma-IFN on the cutaneous fibrotic abnormalities and on lung fibrosis in systemic sclerosis.