To gain further understanding of the pathogenesis of hepatic fibrosis in schistosomiasis, the interaction between egg granulomas and fibroblasts was investigated in an in vitro model. Egg granulomas isolated from livers of mice infected with Schistosoma mansoni or Schistosoma japonicum and cultured in vitro released a nondialyzable substance which stimulated proliferation in resting dermal fibroblasts. The release of the fibroblast-stimulating substance remained relatively constant during the first 48 hr of incubation with granulomas, during which time granulomas remained metabolically active in vitro. A dialyzable molecule(s) in granulomas supernatants interfered with fibroblast uptake of [3H]thymidine in vitro but did not inhibit cellular division. Granulomas supernatants also stimulated fibroblast secretion of prostaglandin E2 and caused an elevation in intracellular levels of cyclic adenosine monophosphate.