A previous study performed in adolescents living in an area endemic for Schistosoma mansoni in Brazil has shown that a 37 kDa schistosome surface antigen is a selective target for antibodies in sera from those who were resistant to reinfection. This antigen was shown by molecular cloning to be the schistosome GAPDH. The aim of the present work was to assess whether peptides corresponding to GAPDH antigenic determinants could be used in a subunit vaccine. Five B cell and two T cell epitopic regions were identified on Sm37-GAPDH. One of the B cell determinants (Sm37-5, aa 268-289) is highly antigenic in human infections and antibody reactivity toward this determinant is associated with resistance to reinfection. Mice and rats immunized with Sm37-5 were partially protected against a challenge infection, indicating that this peptide can induce protective immunity. Analysis of Sm37-5 amino acid sequence indicated that this antigenic determinant is likely conserved among other pathogenic strains of schistosome (S. haematobium, S. intercalatum and S. japonicum), although it shows major amino acid differences with the corresponding human GAPDH sequence. All together these results indicate that Sm37-5 should be considered as a candidate component for an anti-schistosome subunit vaccine.