The accessibility of the surface of human orosomucoid to monoclonal antibodies (MAbs) was investigated by size-exclusion HPLC to examine the validity of its proposed membership in the lipocalin family. The N-terminus half of the molecule contains all the five glycan chains, and of fifty-six MAbs, only one bound to this piece of the polypeptide backbone, indicating that extensive screening was taking place. The simultaneous binding properties of selected MAbs to the fully glycosylated molecule was examined by size exclusion HPLC. The pattern of inhibition was contiguous, with all regions being overlapped. The epitopes of four MAbs having mutual noncompetitive binding were found to be appropriately spaced when placed on a preliminary three dimensional model of orosomucoid. Together, the results support a structure for orosomucoid composed of an exposed continuous protein surface, and a glycan surface screening the remaining protein. Such a structure is provided by the antiparallel β-barrel motif of the lipocalins.