The process of aging results in an increase in collagen in arterial walls, but the blood levels of insulin-like growth factor 1 (IGF-1) decrease remarkably as adults age. There is an almost simultaneous increase in insulin secretion, particularly in obese individuals. It is not known if, under these hormonal conditions, the enrichment of collagen in the arterial wall is due to insulin. We studied the effect of insulin on the production of collagen in vascular smooth muscle cells (VSMC) from elderly persons with high levels of insulin secretion after blocking the insulin receptors with a monoclonal antibody. Results were compared to those without insulin receptor blockage and to those with IGF-1. Despite the inhibition of 14C-glucose uptake, insulin clearly stimulated the release of procollagen III, and increased the collagen synthesis. The hydroxyproline labelling rate from 3H-proline increased to more than twice the control values. IGF-1 is a more potent effector than insulin, but the effect of insulin on the rate of collagen production became similar to IGF-1 when the specific receptors were blocked. The results indicate that under special conditions that occur with aging, insulin interacts with nonspecific receptors in VSMC, especially IGF-1, stimulating these cells to produce collagen.