Chloroform given by gavage in corn oil at 180 mg/kg per day induced kidney tumors in male Osborne-Mendel rats. Chloroform-induced cytotoxicity and regenerative cell proliferation have been observed in the kidneys of male F-344 rats. In order to compare the acute sensitivity of male Osborne-Mendel with F-344 rats, animals from both strains were administered a single gavage dose of 0, 10, 34, 90, 180, or 477 mg/kg chloroform and necropsied 48 h later. Known target tissues were examined for histological changes. Regenerative cell proliferation was assessed as a labeling index (LI, percent of cells in S-phase) as determined by nuclear incorporation of bromodeoxyuridine. The epithelial cells of the proximal tubules of the kidney cortex were the primary target cells for cytotoxicity and regenerative cell proliferation. A dose-dependent increase in the LI was present in the kidney of Osborne-Mendel rats given doses of 10 mg/kg chloroform and above and in F-344 rats given 90 mg/kg and above. The maximal increase in the LI was 4.5- or 3.7-fold over control in Osborne-Mendel or F-344 given 477 mg/kg, respectively. The only increase in the hepatocyte LI was in the F-344 rats given 477 mg/kg. Edema and periosteal hypercellularity were observed in the nasal passages of both strains at doses of 90 mg/kg and above. These data indicate that Osborne-Mendel and F-344 rats are about equally susceptible to chloroform-induced nephrotoxicity. These results provide a basis for linking the extensive data base on mechanisms of action of chloroform toxicity in F-344 rats to the Osborne-Mendel rat and support the hypothesis that events secondary to chloroform-induced cytolethality and regenerative cell proliferation played a role in the induction of renal tumors in the Osborne-Mendel rat.