Human vascular smooth muscle cells (HVSMC) cultured from restenotic lesions are resistant to inhibition of proliferation by heparin. We examined if altered expression of p53 protein might be related to this phenomenon. HVSMC were cultured from saphenous vein and p53 protein levels examined using immunocytochemistry, and by immunoprecipitation with antibodies specific for wild-type or mutant conformations followed by SDS PAGE and immunoblotting. Inhibition of proliferation by heparin was measured in 14-day growth assays. Elevated levels of p53 were found in five out of 41 HVSMC strains. The accumulated p53 protein was not precipitated by a mutant conformation-specific anti-p53 antibody in any of the five strains. In one of the five positive strains there was concomitant human cytomegaloviral infection. No significant difference was found between efficacy of heparin in the p53-positive and -negative strains. Furthermore heparin had no detectable effect on p53 protein levels. Although aberrant levels of p53 are detectable in a minority of HVSMC strains, these data do not support a role for altered p53 expression in resistance to the growth inhibitory effects of heparin in these cells.