The effects of single administration of .DELTA.9-THC [.DELTA.9-tetrahydrocannabinol] on the induction of arylhydrocarbon hydroxylase activity by phenobarbital and 3-methylcholanthrene were determined. .DELTA.9-THC completely suppressed the induction by phenobarbital and reduced the 3-methylcholanthrene induction from 455% to 177% of control. .DELTA.9-THC had no effect on phenobarbital induction when both drugs were administered daily for 2 days and mice killed on the 3rd day. Arylhydrocarbon hydroxylase was not the only enzyme effected as .DELTA.9-THC also inhibited the induction of aminopyrine demethylase by phenobarbital. These drugs do not have any interactive effect on microsomal protein synthesis but are potent antagonists in the synthesis of nuclear RNA.