Abstract. The in vitro formation of the Schistosoma mansoni egg granuloma was examined using transmission and scanning electron microscopy and functional assay of isolated cell populations. This analysis has defined those cells which contribute to the evolution of the granulomatous reaction. Development of the granuloma is analogous to the in vivo process consisting of (1) initial response by macrophages and T lymphocytes, (2) subsequent recruitment of numerous macrophages, lymphocytes, eosinophils, and fibroblasts and, finally, (3) production and deposition of collagen leading to fibrosis in the granuloma. Documentation that formation of the in vitro granuloma closely recapitulates the in vivo process further confirms the potential usefulness of this model in analyzing the physiologic and immunologic mechanisms involved in granulomatous hypersensitivity and fibrosis.