CHCl3 hepatotoxicity was studied in the male Mongolian gerbil and compared to that in the male Sprague-Dawley strain rat. Based on elevations in serum transaminase activities in response to CHCl3 exposure, control gerbils were more sensitive to CHCl3 than were gerbils treated with phenobarbital, chlordecone, mirex, or 3-methylcholanthrene. The increased sensitivity of the control relative to the induced gerbil was consistent with earlier observations of CCl4 hepatotoxicity (Ebel, R. E., and McGrath, E. A., 1984, Toxicol, Lett., 22, 205-210). Microsomal enzyme concentrations or activities were not decreased in the control or induced gerbils in response to CHCl3 exposures of up to 200 microliter/kg. At a dose of 500 microliter/kg, cytochrome P-450 and its reductase were decreased by about 25% in the chlordecone-induced gerbil. In contrast, chlordecone- and phenobarbital-induced rats were sensitive to CHCl3 as evidenced by marked elevations in serum transaminase activities, decreases in microsomal enzyme concentrations or activities, and a transient decrease in hepatic nonprotein sulfhydryl groups. Control rats were insensitive to CHCl3. Histopathological changes in the livers of these animals were consistent with alterations in the biochemical parameters measured. The relationship between sensitivity to the hepatotoxic effects of CHCl3 and CCl4 was different for the gerbil and rat.