Granuloma formation around Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum eggs was compared by the method of von Lichtenberg. Viable eggs were isolated from the tissues of mice after 3 weeks of egg-laying by the worms. The eggs were injected via a tail vein into the lungs of both unsensitized mice and those sensitized by a prior intraperitoneal injection of eggs. The lungs were removed at time intervals from 1 to 96 days after intravenous injection of eggs, sectioned and stained, and the granulomata around the eggs measured. Cross-sensitization among the eggs of the three species was studied. The rate of egg destruction in the tissues was determined by counting the total number of eggs in all of the tissue sections at each time period. Granuloma formation around S. mansoni and S. haematobium eggs was similar temporally, quantitatively, and qualitatively in that there was no reaction around the eggs of either species at 24 hours, the reaction reached its peak at 16 days, and the cellular composition of the lesions was essentially the same. In homologously sensitized animals, reactions to these two species were seen around the eggs at 24 hours, and peak reactivity occurred at 8 days. The granulomatous reaction to S. japonicum eggs was different, in that reactions did occur by 24 hours in unsensitized animals, granulomata were consistently small, cellular composition was somewhat different, and prior exposure to homologous eggs did not result in sensitization. Whereas the reactions around S. mansoni and S. haematobium eggs were apparently immunologic reactions of the delayed hypersensitivity type, those around S. japonicum eggs appeared to be foreign-body reactions similar to those around plastic beads. In relation to cross-sensitization, S. japonicum eggs did not sensitize homologously, so it was not surprising that heterologous sensitization did not occur. Although S. haematobium eggs did not sensitize mice challenged with S. mansoni eggs, it appeared that there was some degree of cross-sensitization in the reverse situation. Finally, the rate of destruction of the eggs of the three species in the unsensitized mouse differed: S. japonicum disappeared most rapidly, followed by S. haematobium, and then S. mansoni. Sensitization increased the rate of egg destruction, although this change did not seem to be due merely to the size and severity of the host reaction.