In murine schistosomiasis mansoni the worm egg-induced granulomatous inflammation is bi-phasic: an initial Th1 type is subsequently switched to a Th2 type response. Analysis of the cellular, molecular base of the Th1-associated response (5–6 weeks post infection) revealed mRNA messages for interleukin (IL)-12 p40, IL-12Rβ2 and interferon (IFN)-γ in the granulomatous livers. When the Th2 type granulomas matured (8 weeks post infection) message expression weakened or became extinct. Macrophages of the Th1 type granulomas produced maximal amounts of IL-12, but production diminished in the mature granulomas. A similar pattern of IL-12 responsiveness of granuloma lymphocytes was observed. In vitro IL-12 production by Th1 type granuloma macrophages was enhanced by tumour necrosis factor (TNF)-α and IFNγ, whereas lymphocyte IL-12 responsiveness was boosted only by TNF-α. Both systems were down-regulated by IL-4 and IL-10 cytokines. Treatment of mice with anti-IL-10 monoclonal antibodies (MoAb) between 6 and 7 weeks of the infection enhanced mRNA expression for IFN-γ and IL-12Rβ2, but not for IL-12 p40. It is concluded that IL-12 and IL-12R expression and function regulate the Th1 phase of the liver granulomatous response. This phase is cross-regulated by type-2 cytokines especially IL-10.