Schistosoma japonicum-infected C57BL/6 mice show similar dynamics of hepatic granulomatous inflammation (HGI) and delayed hypersensitivity (DH) elicited by soluble egg antigens (SEA) which reach peak levels at 9 weeks of infection and then spontaneously regress. The in vitro SEA-induced proliferation of spleen cells (SC) from infected animals attained its high point and then declined when SC from 5-week-infected mice were used. The present study determined the dynamics of interleukin-2 (IL-2) production by SEA-challenged SC from infected mice in an attempt to link the level of IL-2 production to the spontaneous regression of the aforementioned T-cell-mediated immune responses. The production of IL-2 by SEA-stimulated SC reached its peak when cells from 7-week-infected mice were challenged at least 2 weeks after the peak of the proliferative response, but declined at about the same time as the HGI and DH responses. Therefore, the decline in IL-2 activity cannot alone explain the diminished proliferative response but could account for the reduction in HGI and DH in vivo. Some possible mechanisms that might explain the IL-2 deficiency were examined. This deficiency is not due to the in vitro binding of IL-2 by the SC of infected mice and is, therefore, likely to be due to underproduction of IL-2. Nor is the deficiency explained by reduced numbers of antigen-presenting cells (macrophages and B cells) or of L3T4+ T lymphocytes or by suppression of IL-2 production by macrophages or macrophage products such as prostaglandins. However, suppression of IL-2 production was observed consistently upon coculture of SC from acutely infected mice with SC from mice infected for 10 weeks. The cells which suppress appear to be Lyt2+ T cells. The data are consistent with the hypothesis that suppressor T cells inhibit the production of IL-2 and perhaps of other cytokines or lymphokines and that this suppression explains the spontaneous down-regulation of HGI which occurs during schistosomiasis japonica.