To relate the marked differences observed in morbidity due to Schistosoma mansoni infection in the Kangundo and Kibwezi areas of Machakos District, Kenya with possible parasite-related differences in pathobiological characteristics, a quantitative comparison of the host-parasite relationship in infections in NMRI mice with S. mansoni isolates from the 2 areas was conducted. One hundred and 20 cercariae were used per mouse, and necropsy took place between 35 and 94 days following infection. Parameters assessed comprised worm establishment, tissue egg counts, fecal egg excretion, egg production/worm pair, and weights of liver and spleen. Central findings included a higher worm establishment and a lower egg production/worm pair in Kangundo infections than in Kibwezi infections, comparable total tissue schistosome egg counts, and a higher liver/intestinal tissue schistosome egg ratio in Kibwezi infected mice than in the Kangundo infected mice. In addition, a much higher fecal egg excretion, expressed as eggs/g feces and eggs/g feces/worm pair, was observed in mice infected with the Kangundo isolate of S. mansoni than in mice infected with the isolate from Kibwezi. Although possible limitations in the use of mouse models need be realized, the results provide some support to the hypothesis that parasite-related differences in pathobiological characteristics may at least contribute to the marked difference observed in S. mansoni-induced morbidity between the Kangundo and Kibwezi areas.