Abstract: Crosslinking reagents for protein modification are provided, which comprise four functional, leaving groups capable of reacting with amino acid residues on the protein chains, one pair at each end of a relatively rigid chemical spacer group comprising aromatic residues joined by amide linkages. Such crosslinking reagents react with hemoglobin to effect intramolecular crosslinking of two dimeric hemoglobin units to stabilize the tetramers, by use of the respective pairs of functional groups, and to produce dimers of such tetrameric units, i.e. bis-tetrameric, intramolecularly crosslinked and stabilized hemoglobin, to the exclusion of higher molecular weight hemoglobin species.