Anti-Ro/SSA antibodies were determined by a newly developed enzyme-linked immunosorbent assay in serum specimens from 114 patients with systemic scleroderma in order to examine the relationship between Ro/SSA antibodies and clinical subsets of scleroderma. Sera of 42 patients (37%) were positive for Ro/SSA antibodies. Clinical investigations, including Schirmer's test and enzymatic profiles, demonstrated that 60% (16 of 27) of scleroderma patients with sicca syndrome and 63% (10 of 16) with polymyositis (PM) were Ro/SSA positive. In these patients there was a significant association between Ro/SSA antibodies and rheumatoid factor. HLA-antigens DR2, DR3 and B8 showed an increased frequency in anti-Ro/SSA positive patients.