α-Macroglobulin inhibits a broad spectrum of proteinases by forming macromolecular cages inside which proteinases are cross-linked and trapped. Upon formation of a complex with proteinase, α-macroglobulin undergoes a large conformational change that results in the exposure of its receptor-binding domain (RBD). Engagement of this domain by α-macroglobulin receptor permits clearance of the α-macroglobulin: proteinase complex from circulation. The crystal structure of rat α1-macroglobulin RBD has been determined at 2.3 Å resolution. The RBD is composed of a nine-stranded β-sandwich and a single α-helix that has been implicated as part of the receptor binding site and that lies on the surface of the β-sandwich. The crystallographic asymmetric unit contains a dimer of RBDs related by approximate twofold symmetry such that the putative receptor recognition sites of the two monomers are contiguous. By gel filtration and ultracentrifugation, it is shown that RBD dimers form in solution with a dissociation constant of ∼50 μM. The structure of the RBD dimer might mimic a conformation of transformed α-macroglobulin in which the proposed receptor binding residues are exposed on one face of the dimer. A pair of phenylalanine residues replaces a cystine that is conserved in other members of the macroglobulin family. These residues participate in a network of aromatic side-chain interactions that appears to stabilize the dimer interface.