Heterophile antibodies (Ab) against sheep red blood cells were shown to have developed in mice experimentally infected with Schistosoma japonicum (SJ). Incidence of the elevated Ab levels was markedly high in the period of 6–10 weeks following infection. By means of absorption tests, the heterophile Ab could be distinguished from classical human heterophile Ab of Paul-Bunnell, Hanganutzui-Deicher, and Forssman types. Antigen(s) cross-reactive with the heterophile Ab was found only in goat red blood cells (RBC) but absent on RBC of other species, in various tissue homogenates of syngeneic mice, or in SJ parasites and their eggs. The Ab activity seems to be mainly localized in immunoglobulin classes other than IgM.