Red blood cells, serum albumin, and serum lipoproteins transport benzo[alpha]pyrene and other xenobiotic compounds in the circulation. The distribution of benzo[alpha]pyrene and its metabolites among these blood components was examined, and the effect of their presence in the perfusion medium on the ability of isolated livers from 3-methylcholanthrene-pretreated rats to clear circulating benzo[alpha]pyrene was determined. A large fraction (45%) of the benzo[alpha]pyrene in rat blood was associated with the serum lipoproteins. However, only 8% of the benzo[alpha]pyrene metabolites was associated with this component. Forty to forty-five percent of each was associated with red blood cells. Benzo[alpha]pyrene clearance by isolated rat livers was 1.8 +/- 0.2 ml/min when the medium contained only red blood cells and buffer. Addition of serum lipoproteins or serum albumin increased benzo[alpha]pyrene clearance to 5.1 +/- 0.5 or 8.5 +/- 0.9 ml/min respectively. Appearance of benzo[alpha]pyrene metabolites in perfusions medium and bile was similarly altered by the changes in medium composition. These results indicate that the clearance of benzo[alpha]pyrene by rat liver depends on the composition of the medium perfusing the organ and suggest that alterations in blood components in vivo may influence the metabolic disposition of this carcinogen.