Eight baboons (Papio cynocephalus) were percutaneously exposed at 3-month intervals to small numbers of Schistosoma mansoni cercariae until a total of 700 was reached over a 3-year period. Fecal egg excretion in all had passed peak levels and was fairly steady or even depressed by about 40 months after the initial exposure. At this time 5 were challenged with 1,000 cercariae each. The other 3, serving as controls, were killed and their worms were counted. The 5 experimental baboons were killed 175 days after challenge and their worm burdens were determined. Post-challenge fecal egg excretion was not increased over pre-challenge levels. The difference in mean percent recoveries of penetrating cercariae in the two groups (experimental, 28.7%; control, 46.2%) was highly significant (P > 0.99 < 0.999). These data indicate that baboons can acquire immunity to S. mansoni, as reflected in fecal egg excretion and worm burdens. The immunity is partial in that neither are all worms destroyed nor is reproduction terminated in the survivors.