Halothane depresses the metabolism of amobarbital, hexobarbital, pentobarbital, and aminopyrine (type I substrates) by rat hepatic microsomal enzymes. This inhibition is dose-dependent, reversible, noncompetilive, and independent of the lipid solubilities of the substrates. In contrast, the metabolism of aniline (type II substrate) is enhanced by halothane. These actions may represent an effect of halothane on the terminal oxidase of the system, cytochrome P-450.