The prevalence of hypertension and atherosclerosis among subjects with hyperinsulinemia supports the premise of a direct metabolic link between insulin and angiotensin II at the cellular level. In the present study, the effect of insulin on the angiotensin II-induced growth of A10 smooth muscle cells (SMC) was investigated. Treatment of quiescent A10 cells with angiotensin II caused an increase in RNA synthesis, proto-oncogene c-fos mRNA levels and cell size dependent upon pretreatment with insulin. The insulin requirement was independent of its actions as a growth factor, since a pre-treatment of at least 24 h with insulin was essential for growth stimulation by angiotensin II. Using RT-PCR, insulin was shown to regulate AT2 receptor expression in both quiescent and differentiating cells. These data suggest the AT2 receptor, which mediates the growth effects of angiotensin II in A10 cells, may be the critical target for the effect of insulin.