The integrity of the hepatic portal vasculature was examined, relative to the resistance to Schistosoma mansoni observed in 68% of 129/Ola mice. The passage of microspheres to the lungs, following their injection via the superior mesenteric vein, indicated the presence of shunts in the majority of both naive and infected mice. There was a negative association between shunting of microspheres to the lungs and paucity of liver worms at 28/35 days post-infection. Schistosomula accumulated in the livers of resistant mice at a slower rate than in susceptible animals, and after day 21 relocated to the lungs. Many lung schistosomula injected via the superior mesenteric passed immediately to the lungs; the shunts thus greatly reduce the probability of trapping in the liver. Some parasites migrated back from the lungs, successfully lodged in the liver and began to feed on blood. Latex infusion demonstrated the location of large intrahepatic connections between the portal and hepatic veins. We suggest that as these liver worms grow, migrating upstream into progressively larger vessels, they reach the connections, pass out of the hepatic portal system, and relocate to the lungs. The presence of the natural shunts thus accounts for the resistant status of the mice.