Testicular toxicity and interstitial cell tumours induced by cadmium are prevented by zinc or by low dose cadmium pretreatments. The mechanism of this tolerance is unknown, though metallothionein (MT) is thought to play a role in tissue resistance to cadmium toxicity. Thus, the possible involvement of the testicular MT gene in metal-induced tolerance to cadmium toxicity was studied. Rats were pretreated with zinc (1.0 mmol kg-1, s.c.). Histological examination of the testes indicated such pretreatments prevented the necrotizing effects of subsequent doses of cadmium (20 ?mol kg-1, s.c.) administered 24 h later. RNA was extracted from testes or liver 24 h after zinc pretreatment, and analysed by the slot blot technique using the p2A10 cDNA probe to the MT gene. Zinc pretreatment had little effect on MT RNA in the testes, and such pretreatments did not alter testicular cadmium-binding protein capacity. In contrast, RNAs derived from livers of zinc pretreated rats showed marked increases in MT RNA and MT protein. Hence, the testicular MT gene does not appear to play a major role in the induced tolerance to cadmium toxicity and carcinogenesis generated by zinc.