Two populations with differing histories of Schistosoma mansoni and hepatitis C infection were compared directly for severity of disease and extent of comorbidity. Demographic, parasitologic, and ultrasound surveys were conducted on 2038 Egyptians and on 2120 Kenyans. Hepatitis B and C serologies and transaminase levels were obtained from a subset at each site. Despite significantly lower prevalence and intensity of infection, Egyptians had a higher prevalence of severe schistosomal fibrosis than Kenyans (36.8% vs. 4.6%). Hepatitis C infection was 3 times more prevalent among Egyptians, and evidence of hepatocellular damage was significantly greater among Egyptians. There was no interaction between S. mansoni infection or disease and the prevalence or severity of hepatitis C. For both infections, the intensity or prevalence of infection was a poor predictor of morbidity. The prevalence of disease in the Egyptian population from different pathogens suggests a generalized susceptibility to inflammatory liver disease.