Evaluation of portal-systemic shunting in rats from mesenteric and splenic beds. In rats with partial portal vein ligation, 95 +/- 0.9% of the splenic blood flow is shunted from the portal to the systemic circulation when an intrasplenic injection of microspheres is used to determine the degree of shunting. Despite this magnitude of portal-systemic shunting, several biochemical and endocrine consequences of portal-systemic shunting occur at levels below what is expected for the degree of shunting found. In an effort to resolve these discordant findings, shunting from both the splenic and the mesenteric bed was studied in anesthetized portal hypertensive rats with various degrees and/or duration of portal vein stenosis. The shunting from the mesenteric bed averaged 66.7 +/- 29.9% (range 5.1-99.1%) and was influenced both by the degree and duration of portal vein stenosis. In contrast, shunting from the splenic bed averaged 97.3 +/- 4.0% (range 79-99.9%) and demonstrated no variation between groups determined by the degree of portal vein stenosis. The shunting from the splenic bed was consistently greater than that found from the mesenteric bed. Mesenteric but not splenic shunting correlated with serum bile acid levels. Mesenteric shunting was related inversely to the weight-adjusted liver mass and to serum testosterone levels. Based upon these data obtained in portal hypertensive rats, it is concluded that splenic injections of microspheres overestimate portal-systemic shunting. In contrast, mesenteric injections of microspheres yield values for shunting that correlate well with independently determined biochemical and endocrine consequences of shunting. These observations support the validity of the mesenteric shunting measurements obtained. 