The egg-induced granulomatous reaction in Schistosoma mansoni-infected individuals develops within the portal system of the liver and is the major pathological finding in schistosomiasis. We have infected mice lacking the gamma interferon (IFN-gamma) receptor with S. mansoni larvae and studied the development of hepatic granulomas in these mutant mice in comparison to that in control wild-type mice. In the absence of IFN-gamma activity, a dramatic reduction in the size and architecture of the granuloma was observed. Granulomas from mutant mice were smaller than those from the control group and showed a significant reduction in the number of infiltrating inflammatory cells. Moreover, they appear to prematurely progress to the chronic phase of the reaction at a time when the control group still has acute inflammation. Our data suggests a pivotal role for IFN-gamma in the early events of the granulomatous reaction in vivo.