Luicts, GEORGE, SHIRLEY D. BRINDLE AND PAUL GREENGARD: The route of absorption of intraperitoneally administered compounds. J. Pharmacol. Exp. Ther. 178: 562-566, 1971. Although the ip route is widely used for the administration of compounds to animals, it has not been established whether absorption from the peritoneal cavity occurs through the portal or the systemic circulation. This problem has now been investigated in two species by two experimental approaches. The initial(10 seconds to 5 minutes) rates of appearance of radioactivity in the liver and in the systemic circulation of the rat after the administralion of labeled compounds were compared. The substances studied(atropine, caffeine, glucose, glycine and progesterone) represented a variety of physicochemical and biochemical properties. The appearance of radioactivity in the portal vein and in the inferior vena cava of the dog after administration of glucose was also investigated. The results demonstrate that compounds administered ip are absorbed primarily through the portal circulation and, therefore, must pass through the liver before reaching other organs.