Circulating monocytes in 30 patients with progressive systemic sclerosis (PSS, scleroderma) and 28 age and sex matched normal controls were studied. Binding of the lectin peanut agglutinin (PA) was significantly reduced in PSS monocytes (p less than 0.001) together with a reduction in the density of nonspecific esterase staining (p less than 0.001) suggesting advanced maturation. Using monoclonal antibodies to identify cell surface markers, we demonstrated a significant reduction in PSS monocytes bearing the Leu M2 antigen (Mac 120, antigen presenting cells) over controls (p less than 0.05), but were unable to show any differences in the monocyte subpopulations using antisera against Leu M3 and HLA-DR surface antigens. The ectoenzymes 5'-nucleotidase (5'N) and alkaline phosphodiesterase 1 (APD1) were lower and leucine aminopeptidase (LAP) levels were higher in patients with PSS, compatible with immune activation. Interferon-gamma levels in serum did not appear to account for these changes, whereas the levels of Clq binding complexes correlated inversely with the levels of LAP (p less than 0.05). There was a strong correlation between the number of Leu M3 positive cells and the level of the ectoenzyme LAP (p less than 0.001). With increasing disease duration, higher levels of Clq binding complexes were detected (p less than 0.05). These results indicate that monocytes in PSS differ from those in normals and appear to have undergone advanced differentiation and activation changes.