We have been investigating the actions of chloroform (CHC13) and bromodichloromethane (BDCM) in rat kidney after different routes of exposure. Male F344 rats were exposed by gavage with corn oil or water as the diluting vehicle. All experiments lasted 30 days with gavage exposures 5 days per week for 4 weeks (20 doses). All animals were injected IP with bromodeoxyuridine (BrdU) 3 times over a 6-day period at 50 mg/kg/injection. Kidney tissue was fixed and slides were stained with hematoxylin and eosin for routine viewing and by the PAP (peroxidaseantiperoxidase) technique using anti-BrdU to label cells in DNA synthesis. There were no significant changes in gross parameters evaluated between the control rats and the rats exposed to CHCl3 or BDCM. Rats exposed via corn oil gavage to CHC13 displayed a segment-specific epithelial cell necrosis (6/6 high dose, 2/6 low dose). The lesions were primarily localized to the second segment of the proximal tubule, although some spread to cells in the first segment was occasionally observed. No histologic lesions were observed in the kidneys of rats exposed to BDCM.Preliminary results indicate a significant increase in DNA synthesis in the CHCI3-treated rats and a slight increase in DNA synthesis in BDCM-treated rats with corn oil as the diluent. The increase in BrdU labeling was primarily in cells of the S2 segment of the proximal tubule and interstitial cells of CHC13-exposed animals and in cells of the S3 segment of BDCM-exposed animals. The rats exposed using water as the vehicle did not show significant pathology (except for one rat in the high-dose CHC13 group, which had mild necrosis of proximal tubule epithelium). There were no changes in DNA synthesis in the CHCL3-treated rat kidneys when water was used as the vehicle. There was a slight increase in total DNA synthesis in the BDCM-treated rat kidneys, and the increase was mainly in the third segment of the proximal tubule. These data indicate differences in histopathologic alterations and levels of DNA synthesis that appear to depend on the vehicle that the chemicals were dissolved in and/or the route of administration. CHC13-induced pathologic alterations were more severe in the animals exposed by corn oil gavage. BDCM, an established renal carcinogen in rats, failed to induce any histopathologic alterations under the different experimental conditions of this study.