This investigation was conducted to evaluate the effect of gavage vehicles on altering the severity of the subchronic hepatotoxicity of carbon tetrachloride (CCl4). Male and female CD-1 mice were gavaged with 0, 1.2, 12, and 120 mg/kg CCl4 in either a corn oil or 1% Tween-60 vehicle once daily for 5 consecutive days per week for 90 days. The study revealed that the hepatotoxicity was greater in the mid- and high-dose groups of mice that had received CCl4 administered in corn oil. Increases in serum enzyme activities were detected in the mid-dose groups of mice that were gavaged with CCl4 in corn oil. The serum enzyme activities were significantly higher in the high-dose groups of animals in which CCl4 was administered in corn oil. Histopathological findings indicated that hepatocellular changes following the administration of CCl4 at the mid- and high-dose levels were more frequent and more severe when CCl4 was given in corn oil than when it was administered in Tween-60. The experimental findings indicate that the no-observed-adverse-effect level from CCl4 exposure was lowered by an order of magnitude (from 12 to 1.2 mg/kg) and that the hepatotoxicity of CCl4 was enhanced in the high-dose treatment groups when corn oil was employed as the gavage vehicle.