The experimental granuloma system has been further studied by examination of soluble schistosome antigen (SEA) coated bentonite granulomas at 8 and 16 days, at which time epitheloid cells and giant cells were observed confirming the ability of SEA to elicit a true granuloma. The elicitation of delayed hypersensitivity by SEA has been studied in both the mouse foot pad and coated on bentonite particles and latex beads in the mouse lung. In the foot pad SEA elicited an early acute inflammatory response followed by delayed hypersensitivity type dermal response in the sensitized mouse lasting 2 to 4 days. SEA adsorbed to bentonite particles or latex beads elicited a histologically typical granulomatous response in the sensitized mouse lung which peaked at 2 to 4 days and lasted 16 or 8 days respectively. Thus cell response to the same antigen in the same animal differed according to whether it was immediately diffused or was gradually released from a carrier particle, and the duration of the granuloma was proportional to the antigen uptake by the particle. Although SEA release from particles was virtually complete within 60 minutes in vitro, antigen persisted in lung granulomas for at least 24 hours as shown by immunofluorescence. The elicitation of delayed hypersensitivity by SEA was also demonstrated by macrophage inhibition in a micro method using homologous mouse peritoneal macrophages. These findings agree with the hypotheses that delayed hypersensitivity and antigen sequestration are involved in schistosome granuloma formation.