Abstract: In previous studies, species difference in the effect of hexaehloro-p-xylene (HCX) on hepatic drug-metabolizing enzymes was found between rats and mice. In rats, HCX exerted a stimulating effect on drug-metabolizing enzymes, while in mice HCX showed an inhibitory effect. This paper reports the inhibitory effect of HCX on hepatic drug-metabolizing enzymes in guinea pigs.Either a single dose (50～100 mg/kg) or multiple doses (100 mg/kg, qd × 6d or 50 mg/kg, qd×14d) of HCX significantly increased the duration of the hypnosis of sodium pentobarbital. The rate of disappearance of pentobarbital from plasma of guinea pigs pretreated with HCX 100 mg/kg was reduced, and the t 1/2β of pentobarbital in treated guinea pigs was 12.3±2.2 (SD) h, while that in control guinea pigs was 3.8±0.6 (SD)h.The rate of biotransformation of sodium pentobarbital and aminopyrine in hepatic homogenates of guinea pigs pretreated with HCX was reduced significantly.In rats, a single dose (100 mg/kg) of HCX did not affect the ate of disappearance of sodium pentobarbital from plasma. The t 1/2β of pentobarbital in treated and control rats was 3.2 h and 3.1 h, respectively.These results further show that there is a species difference in the effect of HCX on hepatic drug-metabolizing enzymes.