Sera from patients with progressive systemic sclerosis (PSS), compared to normal sera, contained increased fibroblast growth promoting factor(s) (FGPF) for autologous and heterologous PSS skin fibroblasts and fibroblasts from normal donors. The relative stimulatory effect of FGPF was unaltered by dilution, mixing with normal serum, or media refeeding. The mean value of 42 PSS sera tested showed growth promoting activity significantly greater than the mean level of activity obtained with 42 sex matched normals (p less than 0.001). FGPF in sera from 25 patients with rheumatoid arthritis did not differ from normal controls. No correlation was seen between growth enhancement and patient age or medications. FGPF was present in serum plasma and is unlikely from platelets because serotonin and purified platelet factor produced no equivalent growth stimulation. FGPF was nondialysable, heat labile and insensitive to ribonuclease A. Disulphide bond integrity was required since 20 mM dithiothreitol destroyed activity. FGPF was excluded by an XM-50 filter after Sephadex G100 gel filtration.