The present study evaluates the growth promoting effect of insulin on the proliferative activity of cells from rat mesenteric arteries in culture in order to test the hypothesis that insulin may play a pathogenetic role in the hypertrophy of resistance vessels. The proliferative effect of insulin was studied in cultured vascular smooth muscle cells (SMC) obtained from two functionally different rat vessels: mesenteric arteries and aorta. Growth characteristics (cell number and growth rate) of mesenteric and aortic cells were determined after a quiescent period and followed-up for 24, 72, and 120 h after the addition of insulin. At all studied time intervals, aortic SMC exhibited a significatively higher cell number and specific growth rate than did mesenteric SMC. Aortic SMC also displayed a greater proliferation than did mesenteric SMC in the presence of 10% fetal calf serum (FCS). At a physiological concentration of 100 microU/mL, the proliferative effect of insulin, after a quiescent period, was seen only in aortic SMC, at 72 and 120 h. Higher insulin concentration (500 microU/mL) increased significantly the cell number in SMC of both arteries. The proliferative effect was significant at all studied periods for aortic SMC; however, in mesenteric SMC, insulin increased the cell number only at 72 and 120 h. The proliferative effect of insulin was observed on SMC obtained from functionally different arteries such as aorta and mesenteric, being greater in the former. The different behavior of these SMC in the presence not only of insulin, but also of 10% FCS, provides further evidence for the existence of intervascular heterogeneity. The mild stimulatory effect of insulin in vitro may contribute in this way to the vascular hypertrophy of pathological entities exhibiting hyperinsulinemia.