Abstract A novel approach to antigen preparation was applied to the production of neoantigenic antisera against fragment E. An immunoprecipitated antigen was prepared by immunoelectrophoresis of the plasmin digest of human fibrinogen or fibrin against anti-fibrinogen serum. The precipitin bands corresponding to fragment E were cut from agar gels, washed, homogenized and emulsified in complete Freund's adjuvant for injection. The anti-E antisera harvested were absorbed with an immunosorbent column coupled with fibrinogen so that they contain only those antibodies directed against the E-neoantigen. A double antibody radioimmunoassay suggested the presence in these antisera of a population of antibodies which is reactive only with E fragment, but not with native fibrinogen. In addition, the competitive inhibition profile of fibrinogen-E versus fibrin-E showed that some discriminating antisera (especially those derived from the early phase of the immune response) are capable of distinguishing between the two molecular species by differences in their displacement slopes.