Heavy metals are increasingly studied due to their apparent ability to disrupt signaling pathways of living organisms including humans. Among various mechanisms of action, metals are suspected of exerting estrogenic activity in human and wildlife. In this study, a wide range of concentration of cadmium, copper, lead, mercury and zinc (from 95.4 pM to 1 mM) alone or in combination with the natural estrogen, 17-beta estradiol, has been tested using the yeast estrogen screen, an estrogen receptor dependent transcriptional expression assay. No direct trans-activation of the estrogen-responsive element could be measured with any of the concentration of the metals tested. Nevertheless, cadmium, copper and zinc were able to potentiate the estradiol-induced response in a dose-dependent manner. Significant stimulation was obtained from 10 nM cadmium, 100 nM copper and 2 nM zinc. Maximum response led to decrease of the estradiol EC50 by a factor 10. This study indicates that cadmium, copper and zinc can act as potential endocrine disrupters by modulating the estrogenic activity of endogenous hormones.