This brief paper could in no way cover the available literature in this immense and growing field. Some general review articles which list many of the original citations are included (1-3, 5, 9, 17, 28), but no attempt to provide a comprehensive coverage or to include all of the original and incisive papers has been made. Although there are certain important exceptions, most chemical carcinogens are either themselves reactive molecules under physiological conditions or are converted to reactive forms by enzymatic activation. The reactive intermediates form covalent bonds with cellular macromolecules and such interaction represents an initiating event in carcinogenesis. Most investigators now consider DNA to be the critical target molecule in this initiation. This is assumed to be the case for the present discussion, but it is worth pointing out that the combined effects of reaction with DNA and with protein or even RNA are by no means ruled out. Only a small fraction of the known chemical carcinogens are methylating agents, but these are of considerable experimental and environmental importance. Methylating carcinogens such as dimethylnitrosamine (DMN), other methylalkylnitrosamines, and 4-(methyl-