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To define the physiopathological significance of 201Tl per rectum scintigraphy, we compared results obtained using this method with direct measurement of inferior mesenteric shunting, portal pressure, liver cellular function as evaluated by the Aminopyrine Breath Test and the size of esophagogastric varices and spleen, constituting, respectively, indirect representation of azygos and splenic shunts. Results indicated that a high correlation exists between the measures of portal systemic shunt estimated by the per rectal method and those obtained by direct administration of the tracer in the inferior mesenteric artery. No correlation was observed between 201Tl per rectal results and portal pressure or with azygos and splenic shunting. Fair correlation was observed with the Aminopyrine Breath Test. This could be explained by the fact that both methods are altered in advanced liver disease. These results suggest that the 201Tl per rectal scintigraphy explores the portal systemic shunt, which depends almost exclusively on the inferior mesenteric territory. While the limited territory explored by the method constitutes, undoubtedly, a limiting factor in detection and quantitation of total portal-systemic shunt, the specific information provided by the test could be useful in defining clinical and biological profiles of cirrhotic patients with inferior mesenteric shunting.