Intramuscular alpha-interferon improved or stabilized skin score in 10/14 (71%) patients with diffuse cutaneous systemic sclerosis. In 64% of patients, their treating physicians rated it as having stabilized or improved the disease. However, it had no significant effect on grip strength, digital contractures, respiratory function or visceral involvement. Type I collagen synthesis was significantly reduced in fibroblasts cultured from clinically 'uninvolved' skin but not in those from lesional skin. Amino-terminal procollagen III peptides in the interferon treated group were not significantly reduced after 6 months of therapy but showed a trend towards stabilization and reduction compared to disease matched controls on no therapy.