14 C-Labeled gossypol was orally administered to rats. The level of gossypol in the liver reached a maximum 1 day after administration, then decreased with time. Although gossypol was not exclusively segregated in any one cell fraction, most of it was found in the microsomal fraction. Gossypol appeared to distribute according to its lipid-soluble property rather than by virtue of its reaction with protein. In rats fed gossypol, the liver microsomal enzymes which catalyze the oxidative demethylation of p -chloro- N -methylaniline HCl (PCMA) increased in activity. A “no effect” dosage for the stimulation of demethylation of PCMA by dietary gossypol was found to be 50 mg/kg. The gossypol stimulation of rat liver microsomal oxidases seems to be due to an increase in enzyme synthesis since it did not alter the K m (6.7 × 10 −3 m ) but increased the maximal velocity of PCMA demethylation (33%). The ability of rat liver microsomal enzymes to dealkylate some carbamate pesticides was increased by the oral administration of gossypol.