We investigated the cytotoxicity of cadmium in cultured vascular endothelial cells from bovine aorta pretreated with zinc. The cytotoxicity was evaluated by the [ 3 H]adenine release assay. It was shown that the increase in the [ 3 H]adenine release after challenge with cadmium was significantly prevented by pretreatment with zinc. It was histologically observed that cadmium-induced occurrence of the de-endothelialized areas was reduced in zinc-pretreated cell layer. Intracellular accumulation of cadmium was significantly less but that of zinc was more in zinc-pretreated cells. The content of cadmium in both the particulate and the cytosol fraction was decreased by zinc pretreatment; however, metallothionein content after challenge with cadmium was not changed. It was therefore concluded that zinc is capable of inducing a tolerance to cadmium cytotoxicity in cultured vascular endothelial cells; this tolerance is postulated to be due to a decrease in the intracellular cadmium accumulation rather than a metallothionein induction.