Experimental studies in animals have demonstrated that toluene diisocyanate (TDI) is a carcinogen. When rats and mice were exposed orally to commercial-grade TDI (an 80:20 mixture of 2,4- and 2,6-TDI), tumors were induced in both species. The systemic nature of TDI carcinogenicity was demonstrated by the appearance of tumors at multiple sites (pancreas, liver, skin, mammary glands, and circulatory system). Although not statistically significant, rare brain tumors were found in rats exposed to TDI (two gliomas and one pinealoma). Historical controls have a low incidence of gliomas and no reported incidence of pinealomas. Experimental studies in animals have also demonstrated that 2,4-toluenediamine (TDA), a hydrolysis product of 2,4-TDI, is a carcinogen. When rats and mice were exposed orally to TDA, tumors were induced in the livers, skin, and mammary glands of both species. The National Institute for Occupational Safety and Health (NIOSH)concludes that the data on carcinogenicity provide sufficient evidence to warrant concern about the potential consequences of occupational exposure to TDI and TDA. The tumorigenic responses observed in both rats and mice treated with either TDI or TDA meet the criteria of the Occupational Safety and Health Administration (OSHA) Cancer Policy for classifying a substance as a potential occupational carcinogen [29 CFR 1990]. Although the carcinogenic potential of the other TDI and TDA isomers has not been adequately determined, exposure to all TDI and TDA isomers should be reduced. NIOSH therefore recommends that all the isomers of TDI and TDA be regarded as potential occupational carcinogens and that occupational exposures to TDI and TDA be limited to the lowest feasible concentrations. The potential for TDI- or TDA-induced cancer in humans has not been determined, but the risk of developing cancer should be decreased by reducing exposure to TDI and TDA in the workplace.