Three highly purified Schistosoma mansoni egg antigens reactivity with sera from mice with chronic schistosomiasis mansoni (major serologic antigens-MSA1, MSA2, and MSA3) were utilized in radioimmunoassays for determining their stage and species specificity. Inhibition studies revealed that MSA1 was completely stage specific, since its binding to S. mansoni chronic infection serum (CIS) could not be inhibited either with cercarial or adult worm antigen. MAS2 and MSA3 were specific with regard to adult worm antigen but their binding to CIS was slightly inhibited by cercarial antigen. Immature eggs in comparison with mature eggs contained only negligible amounts of MSA1 whereas MSA2 and MSA3 were present in large quantities. Fluid from eggs hatched in spring water (hatch fluid-HF) contained considerable amounts of MSA1 as well as MSA2 and MSA3. With regard to species specificity, MSA1 essentially did not cross-react with crude soluble egg antigen (SEA) from Schistosoma japonicum and Schistosoma haematobium whereas MSA2 and MSA3 showed partial cross-reactivity. Antibody dilution studies with sera from animals and humans infected with heterologous schistosome species (i.e., S. japonicum and S. haematobium) indirectly confirmed the high degree of species specificity of MSA1. The degree of serologic specificity of MSA1 as demonstrated in this study parallels that of the sensitizing activity of S. mansoni eggs and SEA for granuloma formation, as demonstrated in previous investigations. This study, therefore, indicates that MSA1 may be a major immunopathologically active egg antigen. In addition, the high degree of species specificity of MSA1 suggests its use in the serodiagnosis of schistosomiasis mansoni.