Acute hepatic damage in centrilobular or periportal areas was induced in two groups of rats by intraperitoneal injections of bromobenzene or allyl alcohol, respectively. The effect of this zonal damage on the demethylation of 14C-aminopyrine was evaluated by measuring the elimination of 14CO2 in breath following intravenous administration of a tracer dose of the labeled compound. In rats with centrilobular hepatic damage 14CO2 elimination in breath was significantly decreased compared to controls. In rats with periportal hepatic damage, elimination of 14CO2 in breath was unchanged. These results suggest functional heterogeneity of hepatocytes in vivo with respect to drug-metabolizing capacity.