Upon administration of piperine, the major bite factor of black pepper, to male albino rats at a dose of 30 mg (170 mg/kg) by gavage or 15 mg (85 mg/kg) intraperitoneally, about 97% was absorbed irrespective of the mode of dosing. Three per cent of the administered dose was excreted as piperine in the feces. Piperine was not detectable in urine. When everted sacs of rat intestines were incubated with 200-1000 micrograms of piperine, about 47-64% of the added piperine disappeared from the mucosal side. Only piperine was present in the serosal fluid and also the intestinal tissue, indicating that piperine did not undergo any metabolic change during absorption. Examination of the passage of piperine through the gut indicated that the highest concentration in the stomach and small intestine was attained at about 6 h. Only traces (less than 0.15%) of piperine were detected in serum, kidney and spleen from 30 min to 24 h. About 1-2.5% of the intraperitoneally administered piperine was detected in the liver during 0.5-6 h after administration as contrasted with 0.1-0.25% of the orally administered dose. The increased excretion of conjugated uronic acids, conjugated sulphates and phenols indicated that scission of the methylenedioxy group of piperine, glucuronidation and sulphation appear to be the major steps in the disposition of piperine in the rat.