After infection of mice with Schistosoma mansoni, deposition of eggs in the walls of the intestine and liver provokes an intense (acute) T cell response that peaks at week 8 and, thereafter, down-modulates as the disease becomes chronic. Egg antigen-stimulated proliferation of mesenteric lymph node and spleen cells in vitro was intense at week 8 in both IL-10(-/-) and wild-type (WT) mice, while proliferative responses were markedly reduced at week 15 in WT mice, but undiminished in IL-10(-/-) animals. Moreover, in the absence of IL-10 production, levels of both IFN-gamma and IL-4 remained elevated at week 15. Granulomas around eggs embolized in the livers of WT mice were significantly smaller at week 15 than week 8, whereas those in IL-10(-/) animals were larger at week 8, showed no reduction in size at week 15, and were less sharply demarcated by peripheral collagen. There was also a greater leukocytic infiltration and necrosis of the hepatic parenchyma. These data suggest that in mice IL-10 regulates not only the intensity of hepatic inflammation, but also granuloma organization and cohesiveness. It is a crucial agent in the down-modulation of immune responses and immunopathology that defines the transition from acute to chronic disease.