The chronic toxicity and oncogenicity of inhaled toluene were assessed in Fischer-344 rats. One hundred and twenty animals of each sex were exposed for 6 hours/day, 5 days/week, for up to 24 months at concentrations of toluene in air of 0, 30, 100, or 300 ppm. The calculated time-weighted average concentrations for the 24 months of exposure were 0.0, 30.1, 99.7, and 299.0 ppm, respectively. Interim sacrifices on randomly selected animals were conducted after 6, 12 and 18 months of exposure. All surviving rats were sacrificed at 24 months. A large battery of tissues and organs from all animals in the control and 300 ppm toluene group were examined for histopathology. All animals were examined for clinical changes throughout the course of the study and selected animals were used to determine ophthalmologic, hematologic, clinical blood chemistry or urinalysis effects. There were 140 unscheduled deaths over the 2-years study. Gross pathologic examination of rats dying during the course of the study, or that were sacrificed as scheduled, did not reveal any lesions attributable to toluene exposure. Histologically, a variety of proliferative, degenerative and inflammatory lesions were observed in the control and 300 ppm toluene-exposed group. These lesions were considered unrelated to toluene exposure. The results provide no evidence that toluene causes chronic toxicity or oncogenicity in Fischer-344 rats at these concentrations.