Mitogenic activities on confluent fibroblasts by sera from patients with scleroderma and normal controls were studied. In experiments using eight different fibroblast strains (one human fetal lung fibroblast, one foreskin fibroblast, three adult skin fibroblast, and three scleroderma fibroblast), pooled scleroderma serum showed lower mitogenic activity by 3H-thymidine incorporation assay than pooled normal serum. Individual serum investigations revealed that 11 of 33 patients (33%) showed low mitogenic activities; all 11 patients were receiving dipyridamole. Of 15 patients, 11 (73%) receiving dipyridamole showed low mutagenic activities; none of 18 patients not receiving dipyridamole showed low mitogenic activities. Approximately 70% of this serum activity was inhibited by the addition of anti-platelet-derived growth factor (PDGF) antibody indicating that most of this serum activity seemed to be derived from PDGF. Western blot analysis of extracts of normal sera before and after administration of dipyridamole with antihuman PDGF antibody showed a large decrease in the amount of immunoreactive PDGF present. These data indicate that dipyridamole is an effective drug to lower release of PDGF during blood clotting.