Because short in vitro treatments of Chinese hamster cells with 2-aminofluorene and 2-acetylaminofluorene did not increase SCEs even in the presence of a metabolic activation system, experiments were carried out with rabbits to see if in vivo activation occurred. Rabbits injected with 2-AF could activate the compound and a transient dose-dependent increase in SCEs was found in peripheral lymphocytes cultured at various times after the injection. With 2-AAF, however, the response was more variable: some rabbits showed an increase immediately, but one showed an increase only after a subsequent injection. This indicated that among rabbits differences exist in their ability to detoxify 2-AAF. Because rabbits could activate the compounds, in vitro experiments were carried out to see if their lymphocytes responded differently from Chinese hamster cells and to see if the metabolic changes brought about by PHA stimulation affect the ability of the cells to activate the chemicals. The addition of PHA and the consequent metabolic stimulation do affect the induction of enzymes involved in the activation of 2-AF and 2-AAF. Benzo[alpha]pyrene, in contrast, can be activated by rabbit lymphocytes independently of PHA stimulation.