The growth inhibition of in vitro vascular endothelial cell cultures by sera from patients with connective tissue diseases was studied. Seven out of 30 sera from patients with progressive systemic sclerosis (PSS) exhibited a cytotoxic effect. The cytotoxic serum factor(s) was not specific to patients with PSS, it was also demonstrated in sera from patients with other connective tissue diseases with vascular symptoms (11 out of 27 sera from patients with a mixed connective tissue disease, MCTD; 5 out of 34 sera from patients with a systemic lupus erythematosus, SLE). The cytotoxic effect was not specific for vascular endothelial cells, it was also found on fibroblast cells cultures. Inhibitor(s) of cell growth in vitro was independent of antinuclear and anticytoplasmic antibodies and appeared as a common feature of all connective tissue diseases with vascular symptoms.