Black pepper (Piper nigrum L.) among several irritating spices tested was highly effective on the duration of hexobarbital hypnosis in mice. Pretreatment of mice with the methanolic extract of black pepper (60mg/kg i.p.) prolonged markedly the duration of hexobarbital sleeping time. Three consecutive daily administrations of the same dose of black pepper extract, however, shortened (37%) the duration of hexobarbital sleeping time. The ether soluble fraction of black pepper extract caused most potent effects on the duration of hexobarbital hypnosis. From the above results, it was postulated that the lipid soluble components of black pepper might considerably change the drug action and metabolism by altering drug metabolizing enzyme systems.