B6C3F1 mice and Sprague-Dawley rats were provided drinking water containing 6 - 31 mM trichloroacetic acid (TCA), 8 - 39 mM dichloroacetic acid (DCA) or 11 - 33 mM monochloroacetic acid (MCA) for 14 days. TCA and DCA, but not MCA, increased the mouse relative liver weight in a dose dependent manner. Rat liver weights were not altered by TCA and DCA treatment, but were depressed by MCA. Hepatic peroxisome proliferation was demonstrated by increased palmitoyl CoA oxidase activity (PCO), appearance of a peroxisome proliferation-associated (PP-A) protein, and morphometric analysis by electron microscopy. Mouse peroxisome proliferation was enhanced in a dose dependent manner by both TCA and DCA, but only the high DCA concentration (39 mM) increased rat liver peroxisome proliferation. MCA was inactive in both species. Three other mouse strains (Swiss-Webster, C3H, and C57BL/6) and two strains of rat (F344 and Osborne-Mendel) were examined for sensitivity to TCA. TCA (12 and 31 mM) effectively enhanced peroxisome proliferation in all mice strains, especially the C57BL/6. A more modest enhancement in the Osborne-Mendel (288%) and F344 rat (167%) was seen. Dosing F344 rats with 200 mg/kg TCA in water or corn oil for 10 days increased peroxisome proliferation 179% and 278% respectively above the vehicle controls. Corn oil potentiated the TCA effect (316% above the water vehicle). (Copyright (c) 1989 by Academic Press, Inc.)