Liver fibrosis in schistosomiasis is associated with prominent accumulations of fibroblasts. Primary cell cultures were prepared from the fibrotic livers of Schistosoma mansoni-infected mice, and cells with the appearance of fibroblasts by light microscopy were isolated from these cultures. Proliferation of these cells was examined in coculture experiments with syngeneic inflammatory cells. T cell-enriched mononuclear cells from spleens of S. mansoni-infected or normal mice, and Kupffer cell/macrophages from fibrotic liver all stimulated the proliferation of liver fibroblasts, as measured by 3H-thymidine uptake. Primary cultures of mouse skin fibroblasts showed similar responses to coculture, but an established fibroblast line, 3T3, was unresponsive. Cell-free supernatant medium from coculture experiments did not affect fibroblast proliferation, perhaps because of the requirement for serum in the culture medium. Liver fibroblasts derived from this disease model may be especially suitable for study of the interaction between tissue inflammation and fibrosis.