Structurally unrelated peroxisome proliferators induce altered areas (AA), neoplastic nodules (NN), and hepatocellular carcinomas (HCC) in rats and mice. In this study we have examined several AA, NN, and HCC induced by Wy-14,643 and ciprofibrate in rats for gamma-glutamyltranspeptidase (GGT) and the placental form of glutathione S-transferase (GST-P) by histochemical and immunohistochemical procedures, respectively. In Wy-14,643-treated animals 96-100% of NN and HCC was negative for both GGT and GST-P. Eighty-seven % of the AA was negative for both GGT and GST-P, and only 2% was positive for both the marker enzymes. In ciprofibrate-treated animals 52% and 75% of AA were negative for GST-P and GGT, respectively, and 16% was positive for both the enzymes. However, a large majority of NN and HCC (more than 95%) was devoid of both these marker enzymes. Thus these studies clearly indicate that the hepatic lesions induced by peroxisome proliferators display different phenotypic properties as compared to the lesions induced by commonly used classical liver carcinogens. We conclude that GGT and GST-P are not the ideal markers for identifying AA, NN and HCC induced by peroxisome proliferators.