The mechanisms of inhibition by simultaneously administered phenobarbital of 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB)-induced hepatocarcinogenesis in the rat were studied. Weanling rats were fed a diet containing 0.06% 3'-Me-DAB or 0.06% 3'-Me-DAB and 0.05% phenobarbital for 3 weeks, followed by either basal diet or a diet containing 0.05% phenobarbital as a promoter. The number and the size of enzyme-altered islands and the number of tumors larger than 5 mm in diameter were scored at week 12 and week 40, respectively. The simultaneous feeding of phenobarbital and 3'-Me-DAB resulted in a significant decrease in the number and size of enzyme-altered islands and in the number of tumors, in comparison with those scored in animals fed 3'-Me-DAB alone. It was concluded that the simultaneous feeding of phenobarbital inhibits both the initiation of carcinogenesis and also the promotive action of the carcinogen resulting from its selective toxicity on the liver tissue.