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The conformation of the carboxy-terminal aspects of the Aα chain of human fibrinogen has been assessed by immunochemically characterizing the Aα 239 - 476 and Aα 518 - 584 regions of the molecule. Two peptides, corresponding to these regions, were isolated from cyanogen bromide digests of the Aα chain by molecular exclusion and high-performance liquid chromatography. Each pep tide reacted with antibodies elicited by immunization with the Aα chain and intact fibrinogen. Aα 239 - 476 appears to be a relatively immunodominant region of the molecule. Competitive inhibition analyses confirmed the accessibility of these regions to antibody in native fibrinogen. Each peptide, however, contained one or more epitopes, which was occult in the native molecule. These occult epitopes were expressed by the intact Aα chain and became accessible when fibrinogen was cleaved with plasmin. With plasmic degradation the epitopes expressed by fibrinogen and contained within these two peptide regions became significantly more reactive with antibody. This change occurred in concert with release of the Aα 518 - 584 region from the core of the molecule but did not require the generation of free Aα 239 - 476. Ultimately the epitopes within both regions were shed from the plasmic-resistant core of fibrinogen. Peptide epitopes were expressed in a similar manner by prolonged plasmic degradation of fibrinogen and fibrin with α chain cross-linking. These results are generally consistent with models depicting the carboxy-terminal aspects of the Aα chain as being surface-oriented but suggest a systematic ordering of structure when these regions are integrated into the native molecule. Plasmic cleavage significantly relaxes the conformational restraints on the organization within this region. [ABSTRACT FROM AUTHOR]