Recombinant DNA techniques were employed to address the problem of specificity in a serodiagnostic test for schistosomiasis. Immunoprecipitation of in vitro translation products of adult Schistosoma mansoni RNA with sera from Egyptian donors revealed that the human IgG response to schistosome proteins is highly heterogeneous, does not correlate with clinical status, and remains essentially unaltered 6 months after chemotherapeutic cure; peptides of 38 and 70 kDa are recognized by sera from patients infected with S. mansoni or S. haematobium but not by sera from individuals harboring other helminth infections. Using serum from C57BL/6J mice acutely infected with S. mansoni, which strongly reacts with these peptides and very weakly with other worm proteins, portions of the 70 kDa peptide were cloned from an expression cDNA library. The value and limitations of using recombinant schistosome antigens in serodiagnostic assays is discussed.