Increases in the use of methanol (MeOH) as a transportation fuel would result in greater potential for inhalation exposure. Because oral exposure to MeOH potentiates the hepatotoxicity of carbon tetrachloride (CCI4), we examined the ability of inhaled MeOH to potentiate CCI4hepatotoxicity and the time course of injury and recovery. Adult male F‐344 rats were exposed to 0 or to 10,000 ppm MeOH by inhalation lor 6 h and gavaged with 0.075 ml CCI4/kg 24 h later. Hepatotoxicity was assessed 0.5, 1, 1.5, 2, 3, 7, 15, 30, and 61 d after CCI4exposure. For CCI4alone, hepatotoxicity was most severe at 0.5 and 1 d, when minimal centrilobular hepatoceltular necrosis and predominately mild centrilobular hepato‐cellular vacuolar degeneration occurred. By d 3, the livers from the CCI4rats were histo‐logically normal. For MeOH + CCI4, peak seventy of hepatic injury was at 1 and 1.5 d, when moderate centrilobular necrosis and moderate/marked centrilobular degeneration occurred. MeOH + CCI4resulted in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that were increased, relative to CCI4alone, 171‐ and 113‐fold, respectively, on d 1, and 166‐ and 140‐fold, respectively, on d 1.5. Significant serum elevations in MeOH + CCI4rats, relative to CCI4alone rats, were present until d 7 and d 15 for AST and ALT, respectively. By d 3 and d 7, degeneration and necrosis, respectively.