Peripheral blood lymphocytes isolated from 19 patients with progressive systemic sclerosis (7 with diffuse scleroderma and 12 with CREST syndrome) and from 19 healthy control individuals were tested in a lymphocyte-induced angiogenesis assay. The cells were injected intradermally into x-ray-immunosuppressed mice and their capability to induce new blood vessel formation was assessed by morphologic criteria. The lymphocytes derived from patients with systemic scleroderma showed a significant decrease in angiogeneic capability compared with controls. No significant difference in this capability was found between patients with diffuse scleroderma and those with CREST syndrome. The decrease in the angiogeneic capability of lymphocytes reflects a depression in cell-mediated immunity and might be relevant to the capillary loss observed in systemic scleroderma.