Abnormalities in the regulation of proliferation of vascular smooth muscle are believed to be involved in the development of atherosclerosis. This study addresses the question of whether altered levels or activity of circulating factors in diabetes may influence the growth of vascular smooth muscle cells and fibroblasts. Plasma prepared from a group of patients with insulin-dependent diabetes mellitus was less capable of stimulating DNA synthesis in cultured vascular smooth muscle cells and human lung fibroblasts than plasma from control subjects. In contrast a platelet lysate prepared from the same patients caused significantly greater DNA synthesis than did a platelet lysate prepared from the controls. Thus both increased and decreased growth promoting activity exist in diabetes. The end result of these abnormalities may depend on the sensitivity of the target organ and platelet function, but may be related to the increased risk of atherosclerosis amongst the diabetic population.