AbstractSubacute toxicity of trichloroethylene (TCE) was evaluated in male and female B6C3F1 mice using corn oil or aqueous gavage vehicles. Mice received oral doses of TCE five times a week for 4 weeks at 600, 1200 and 2400 mg/kg/day for males and 450, 900 and 1800 mg/kg/day for females. Vehicle control mice were dosed with either corn oil or a 20% aqueous solution of Emulphor. A dose‐related increase n lethality occurred in male and female mice receiving TCE in Emulphor but not corn oil during the first week of treatment. Lethality was consistent with central nervous system depressant effects of TCE. After 4 weeks of exposure, body weights were not altered by TCE but liver/body weight ratios were uniformly increased by TCE administered in either vehicle in both sexes. Only male mice treated with TCE in corn oil, however, sustained elevations in serum enzyme levels, accompanied by liver histopathology. TCE in corn oil produced inflammation‐associated focal necrosis in 30–40% of the male mice, with increasing severity from low to high dose. Lipid accumulation, as indicated by Oil‐Red O staining, was most prevalent in male mice treated with TCE in corn oil but also occurred to a lesser degree in animals receiving either gavage vehicle alone. This study indicates that the type of oral gavage vehicle is an important factor in determining the nature of TCE t