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The role of L3T4+ and Lyt2+ lymphocytes in the formation and modulation of granulomas around Schistosoma japonicum eggs was examined in athymic mice. Nude C57BL/6 mice infected with S. japonicum miracidia were compared to nude mice given normal spleen cells depleted of L3T4+ or Lyt2+ cells prior to infection and to intact mice. Nude mice formed small granulomas that were poor in eosinophils and connective tissue. Nude mice reconstituted with cells enriched for L3T4+ or Lyt2+ cells formed granulomas similar in size to those in intact mice, but granulomas in mice given Lyt2+ cells contained few eosinophils and had significantly less collagen than did granulomas in mice given L3T4+ cells. The same was true at 10 weeks. Mice reconstituted with null cells were examined at 7 weeks and formed granulomas similar to those in mice given Lyt2+ cells. By 10 weeks after infection, granulomas had decreased to the same minute size in all groups of mice. Fibrosis increased at weeks 7–10 in all groups of mice.