The effect of antioxidants on the proliferation of cultured endothelial cells (ECs) were studied. Probucol, a lipid-lowering drug with antioxidant properties, added to the growth medium stimulated the proliferation of ECs. D1-alpha-tocopherol (tocopherol), a natural antioxidant, and butylated hydroxytoluene, a synthetic antioxidant also had the same effect on the proliferation of ECs. There was no significant difference in the content of thiobarbituric acid-reacting substances between the probucol-containing growth medium and control medium during the growth assay. Pretreatment of ECs with probucol or tocopherol also enhanced ECs proliferation in medium without any added antioxidants. The addition of free radical scavengers superoxide dismutase, catalase and mannitol to the growth medium did not enhance the proliferation of ECs. These findings indicate that the stimulatory effect on ECs proliferation of antioxidants in the growth medium appears to be unrelated to preventing free radical reactions in the medium itself, but rather may be related to the uptake of antioxidants by ECs.