Changes in the surface antigenicity and susceptibility to eosinophil-dependent killing during in vitro development of schistosomula of Schistosoma mansoni, were examined using sera from rabbits and mice immunized with antigens that are shed from the schistosomulum in vitro (shed antigen), a carbohydrate extract of shed antigen (SAg/CHO) or a periodate-insensitive fraction of shed antigen (SAg/PEP). Anti-SAg/CHO antisera recognised mainly carbohydrate epitopes on the parasite surface, whilst anti-SAg/PEP antisera bound to periodate-insensitive, putative peptide, surface epitopes. Anti-SAg/PEP antibodies failed to recognise the surface of newly transformed schistosomula unless the parasite was first treated with sodium periodate, suggesting that these epitopes may be masked by periodate sensitive (i.e., carbohydrate) epitopes. There was an increase in anti-SAg/PEP antibody binding to the larval surface with age of the parasite in vitro; five-day-old lung schistosomula were also recognised by anti-SAg/PEP antisera. In contrast, anti-SAg/CHO antibody binding declined with parasite age, and failed totally to recognise lung schistosomula. This change in epitope expression was reflected in eosinophil-dependent cytotoxicity assays, with anti-SAg/CHO antisera killing young larvae and anti-SAg/PEP antisera only killing older larvae. Lung worms were not killed by either antisera. The difference in epitopes recognised by the antisera was also reflected in the antigens identified by immunoprecipitation and SDS-PAGE.