Impairment of cell-mediated immunity has been described in chemically-induced as well as mutation diabetes in the mouse. The present report examines the host-parasite relationship during the acute phase of schistosomiasis mansoni in the mutation diabetic mouse (db/db). Cercarial penetration and maturation and egg output by adult worms were similar in the db/db mice and their littermate controls (db/+). In contrast, the pathological consequences of schistosomiasis were much less in the db/db mice. The mean liver weight computed as a percentage of body weight in db/db mice was 4.6 ± 0.2 and following 8 weeks of infection it was 5.7 ± 0.3 (difference is not statistically significant), whereas in infected db/+ mice it was 7.2 ± 0.5. Infection in db/+ mice increased their mean portal pressure by 124% in contrast to an increase of only 12% in db/db animals. The most striking difference was noted in the mean granuloma diameter in the liver: 402 ± 35 µm in db/+ in comparison to 147 ± 10 µm in db/db mice (P < 0.001). This study demonstrates the crucial role of the host granulomatous response in the causation of disease due to Schistosoma mansoni. Furthermore, it underlines the decreased pathological consequences when the host granulomatous response is suppressed, which can be compared to the response of modulated animals with chronic schistosomiasis.