It is now well established that the granulomatous inflammation surrounding the eggs of Schistosoma mansoni is mediated by Th lymphocytes. Our laboratory has recently cloned murine CD4+ Th cells specific for schistosomal egg Ag (SEA). In the current study, SEA-specific IL-2-producing Th1 clones were tested for their ability to mediate local delayed-type hypersensitivity (DTH) reactions, as well as granuloma formation in vivo. Marked delayed-onset erythema and induration developed in footpads of normal syngeneic hosts injected with SEA together with SEA-specific Th1 clones. Histologic examination of these lesions revealed typical, predominantly mononuclear, cell infiltrates characteristic of DTH reactions. Conversely, no reactions were observed in allogeneic hosts, in the absence of SEA, or with the use of a control Th1 clone. Moreover, adoptive transfer of cloned SEA-specific Th1 cells to normal syngeneic mice mediated, in 4 days, the formation of vigorous granulomas around schistosomal eggs embolized in the lungs. Such granulomas, which were quantitated by computer-assisted morphometric analysis, were comparable in size to those elicited by lung-embolized eggs in SEA/CFA-immunized mice. In contrast, significantly smaller granulomas were observed in normal recipients of eggs plus a control Th1 clone or of eggs alone. Our data indicate that Ag-specific, MHC-restricted, local DTH reactions, as well as egg granuloma formation in vivo, can be mediated by monoclonal SEA-specific Th1 cells. They suggest that T cell sensitization to only small numbers of SEA determinants may be sufficient to elicit the hepatointestinal granulomatous inflammation associated with schistosomiasis.