A major surface antigen of Schistosoma mansoni has been identified and characterized as a glycoprotein of 66,000 molecular weight (Mr) and isoelectric point of 6.2–6.1 (SM66-GP) by use of a monoclonal antibody. The antigen was expressed by schistosome eggs, cercariae, larvae, and adults, and was recognized by sera of schistosome infected hosts. Direct immunofluorescence microscopy showed the antigen was distributed in a uniform pattern on the entire worm surface. Indirect immunofluorescence microscopy revealed that it was present in the parenchymal tissue of immature and mature Fasciola hepatica, in the gut of the mature fluke, and in embryonated fasciola eggs. The crossreactive F. hepatica epitope recognized was expressed on a polypeptide of Mr 220,000.