The human platelet receptors for normal, nonimmune IgG and its F(ab')2 and Fc fragments were studied by the use of a cleavable, bifunctional, photoactivable, 125I-labeled cross-linking agent. Derivatization of the ligands with N-[4-(p-azido-m-[125I]iodophenylazo) benzoyl]-3-aminopropyl-N'-oxysuccinimide ester (Denny-Jaffe reagent) reduced their binding to platelets by greater than or equal to 20%. Cleavage of the azo linkage of the Denny-Jaffe reagent, which splits the molecule so that its 125I-labeled portion becomes associated with the receptor half of the cross-linked ligand-receptor complex, was utilized to directly identify receptors for the various immunoglobulin ligands. Specificity of the binding reaction could be demonstrated by suppressing the iodination of the receptors with excess nonderivatized ligand. Two principal IgG-related receptors could be identified by high-resolution NaDodSO4/PAGE and subsequent analysis of the electrophoretically transferred peptides to nitrocellulose filters for localization of radioactivity and immunological characterization. Intact monomeric IgG and F(ab')2 fragments derived from it appeared to have the glycoprotein IIIa as the major receptor, whereas Fc fragments bound predominantly to a peptide of Mr approximately 200,000 (Mr, approximately 50,000 under rigorous reducing conditions).