Excretory-secretory (E-S) products obtained during in vitro Schistosoma mansoni miracidium-to-sporocyst transformation were found to contain a 108-kDa polypeptide capable of scavenging both exogenously produced and M-line Biomphalaria glabrata hemocyte-derived superoxide (O2-) anions. Separation of crude transformation E-S products using HPLC and ion exchange chromatography resulted in the separation of two isoforms of the 108-kDa molecule. Using an in vitro phagocytosis assay, both isoforms were found to be capable of reducing O2- production by phagocytically stimulated M-line B. glabrata hemocytes without cell loss and without a concomitant reduction in phagocytosis. Although parasite antioxidant molecules appear to play a role in the evasion of host oxidative defense systems in several parasite-vertebrate systems, no previous reports of a parasite antioxidant capability against the potential of oxidative killing by invertebrate defense systems has been reported. In conjunction with the previously confirmed production of O2- by B. glabrata hemocytes and reports of reactive oxygen metabolite production by hemocytes from several molluscan species, these results indicate that reactive forms of oxygen and parasite antioxidant systems may play an important role in the determination of compatibility in the trematode-mollusc relationship.