In establishing "safe" standards for all with respect to environmental carcinogenesis, one must consider the heterogeneity of man. Although cancer is considered primarily an environmental disease, there is a wide range of geneticqnvironmental interaction which ultimately influences the development of malignant disease. Considerations of subgroups susceptible to environmental carcinogenesis requires consideration of mechanisms of carcinogenesis. It appears that most carcinogens are mutagens, and that carcinogenesis may be viewed as a multistage process. If mutation is an essential step in the carcinogenic pathway and more than one step is required, then susceptibility to malignancy following mutagen exposure may be affected either by variation in the probability of mutation or variation in the number of necessary mutagenic events. In addition, the probability of malignancy following a mutational event may be influenced by variation in promotional factors acting at each step. Many different disorders may affect the frequency of mutational events within specific tissues. Tissue specific aberrations in growth control due to an intrinsic increased mutation rate, excessive promotional or growth stimulating factors (neurofibromatosis?), or chronic stimulation due to failure of feedback control mechanisms (immune deficiency syndromes?) may lead to tissue specific increased mutation rates, or increased cell proliferation and thus increased numbers of cells at risk. Exposure of tissues with a high mutation rate to mutagens increases the probability not only of the first mutation, but also of subsequent mutations leading to malignancy. Disorders characterized by chromosomal instability or increased mutagenesis in vivo or in vitro