Selenium, an essential trace element, can also be toxic at higher levels of exposure. Several lines of evidence show epigallocatechin-3-gallate (EGCG), a predominant component of green tea catechins with numerous health benefits, can ameliorate the toxicity of many agents. A proof-in-principle experiment was conducted to determine if EGCG would ameliorate sodium selenite-induced growth suppression. Mice were intraperitioneally injected with selenite once daily for five days at a dose of 3 mg Se/kg, which fully suppressed animal growth but did not cause death. Surprisingly the co-administration of the selenite and nontoxic doses of EGCG (10, 20 and 40 mg/kg, intraperitioneally) resulted in the mortality of treated mice in a dose and time-dependent manner (33.3%, 100% and 100%, respectively). EGCG-selenite induced lethality did not result from enhanced selenium accumulation but appeared to involve the suppression of a selenite-induced adaptive response as evidenced by hepatic glutathione S-transferase activity. While EGCG has been reported to ameliorate the toxicity of some agents, the induction of mortality by combined treatment with pharmacological doses of selenium and EGCG is a previously unrecognized synergism that must be considered not only in the remediation of high environmental selenium exposures but also in the development of pharmaceuticals and nutriceuticals.