Abnormalities of growth regulation in arterial smooth muscle cells (SMC) are important in the pathogenesis of vascular disease. Recent studies have demonstrated an accumulation of polyploid SMC in hypertensive, and to a lesser extent in normotensive, arteries. The aim of this study was to evaluate the intrinsic genetic predisposition of aortic SMC from spontaneously hypertensive rats (SHR) to become polyploid in response to in vitro growth stimulation. Flow cytometry revealed that in vitro polyploidization was greatest in Wistar-Kyoto rats (WKY, normotensive inbred rats genetically related to SHR), intermediate but high in SHR and lowest in outbred (Sprague-Dawley) and genetically unrelated inbred (Fischer) rats (P less than 0.001). No differences were observed between neonatal and adult animals of the same strain; non-arterial WKY cells remained diploid. Reproductive clonal populations of polyploid SMC could be isolated from early-passage cultures of SHR and WKY cells. These studies suggest intrinsic differences in in vitro polyploidization among different rat strains, and may improve understanding of SMC growth control.