The effects of cadmium, an environmental toxin present in tobacco smoke, were studied in vitro in human monocytes and compared to those of tobacco smoke. Overexpression of the 72kDa heat shock/stress protein Hsp70 and cell death occurred with a similar time-course and to a similar extent in human monocytes exposed to either cadmium or tobacco smoke. Cadmium and tobacco smoke-mediated toxicity were associated with a decrease in the cellular content of glutathione and ATP and the glutathione precursor N-acetyl-L-cysteine prevented both cadmium and tobacco smoke-mediated toxicity. Furthermore, tobacco smoke-mediated toxicity was prevented by pretreatment with the cadmium chelator resin Chelex-100, supporting the conclusion that cadmium plays a major role in tobacco smoke-mediated toxicity.