Age-related changes in drug metabolism of the liver from male Lou rats were determined by measuring changes in the production of mutagens. Activation of aflatoxin B1 (AFB1), 2-aminoanthracene (2AA) and benzo[a]pyrene (B[a]P) to mutagenic derivatives was assayed using the Ames salmonella test system. The promutagens were incubated with tissue fractions isolated from rats ranging in age from 3 weeks to 18 months. Hepatic activation of AFB1 and 2AA changes with age and is maximal from 4 to 10 months. In contrast, no significant modification with age was observed for the activation of B[a]P. It is concluded that the composition of different cytochrome P-450 fractions is modified with age thereby altering the specific ability to convert different promutagens to mutagens.