Acetone potentiation of haloalkane-induced hepatotoxicity is well recognized. Others reported that trichloroethylene (TCE) can potentiate the hepatotoxicity induced by CCl4. The purpose of the present study was to determine if acetone (A) can potentiate the hepatotoxicity of haloalkane (HA) mixtures. We derived dose-response curves for the potentiation of TCE, CCl4, and TCE-CCl4 induced hepatotoxicity by acetone. Male Sprague-Dawley rats received acetone (0.25-1.5 ml/kg, po); 18 hr later, they received an ip injection of either TCE, 0.25 ml/kg; CCl4, 0.1 or 0.6 ml/kg; or a mixture of TCE and CCl4. Rats were killed 24 hr later, the livers excised, and plasma ALT activities and bilirubin concentrations determined. Histological evaluations were also performed. Neither A, TCE, or both in combination modified the biochemical indices. Acetone potentiation of CCl4-induced liver injury was greater than TCE-potentiation of CCl4. Acetone enhanced the hepatotoxic response of the TCE-CCl4 mixture. Thus, CCl4-induced hepatotoxicity was enhanced by the simultaneous administration of TCE, and this response was potentiated by the previous administration of acetone.