Smooth muscle cell (SMC) growth may play an important role in the pathogenesis of vascular diseases such as atherosclerosis and hypertension. Recent studies have demonstrated that, under different growth stimuli in vivo, SMC may respond by proliferation of diploid cells, polyploidization to the tetraploid (or even octaploid) state, or both. In this study, we used flow cytometry to evaluate the intrinsic tendencies of aortic SMC and nonarterial cells from rats of different strains, ages, and blood pressures to polyploidize in response to in vitro growth stimulation. Significant strain-related differences in polyploidization of aortic SMC were found (P less than 0.001): highest in WKY (normotensive inbred rat related to SHR), intermediate in SHR (genetically hypertensive rat), and lowest in Sprague-Dawley and Fischer (normotensive outbred and inbred rats). Animal age had less or no effect on the degree of polyploidization. Nonarterial cells (venous SMC and lung cells) from WKY and SHR remained essentially diploid, suggesting tissue specificity of in vitro polyploidization. Studies of the growth kinetics of uncloned and clonal populations of aortic SMC revealed decreased proliferation as the ploidy increased in WKY, SHR, and Sprague-Dawley. These findings suggest that genetic strain factors as well as cell type/site of origin significantly influence in vitro polyploidization, whereas animal age and blood pressure do not. The findings also emphasize the need to consider ploidy changes when evaluating in vitro SMC growth kinetics. Further studies will improve understanding of SMC growth regulation and the functional significance of vascular polyploidy.