A variety of drugs produce an inhibition of the in vitro and in vivo metabolism of pentobarbital, hexobarbital, meprobamate, carisoprodol and strychnine and most of these drugs produce after 36–48 hr a stimulation of the in vitro and the in vivo metabolisms of pentobarbital et al. On the other hand, a number of drugs, known as the stimulator of the microsomal drug-metabolizing enzymes, produce an inhibition of these enzymes, if they are added directly to the incubation mixture or given to the rats shortly before the administration of pentobarbital et al. It would therefore appear that many drugs cause the biphasic effects on the microsomal drug-metabolizing enzymes, chlorcyclizine, phenaglycodol, thiopental, hydroxyzine, benadryl, zoxazolamine, phenylbutazone, SKF 525A, DPEA, MG 3062. There is no direct relationship between these effects and glutethimide, phenaglycodol and thiopental stimulate the drug metabolism more markedly than SKF 525A, DPEA and MG 3062, and the latter compounds inhibit the drug metabolisms more markedly than the former. Phenobarbital, meprobamate and urethan have strong stimulatory action, but they have no or only very weak inhibitory action, while JB 516, ipronizaide, imipramine and azacyclonol have strong inhibitory action, but they have no stimulating action. The results of the present studies are of practical importance in the evaluation of the action of two compounds administered simultaneously or after short time intervals.