Addition of wheat germ agglutinin (WGA) (50 ug/ml) to washed human platelets (3 x 108/ml) resulted in platelet activation and the release of l4C-5HT within the same time scale as 0.05 units/ml thrombin. In contrast, succinyl-WGA (100 ug/ml) induced no platelet response. The increased valency of WGA (4) compared with succinyl-WGA (2) suggests that the activation is induced through the cross-linking (immobilisation ?) of closely associated receptors in the membrane. This finding induced us to attempt to cross-link and thereby identify adjacent molecules in the membrane by “near-neighbour” analysis. Constituent -SH groups were oxidised employing Cu2+/phenanthroline or diamide as catalysts, and polymers formed as a result of intermolecular -S-S- formation between adjacent molecules were identified by SDS-PAGE. Although previous reports have shown that the major human platelet membrane glycoproteins contain -SH groups, no apparent cross-linking of the glycoproteins was located following the incubation of either washed platelets or isolated membranes with Cu2+/phenanthroline or diamide. However bidimensional SDS-PAGE (1st dimension non-reduced, 2nd dimension reduced) showed the presence of several protein polymers including complexes formed by the cross-linking of 3 large polypeptides of M. Wt. 250 000, 220 000 and 200 000. These components were easily eluted from membrane vesicles at pH 10 and may represent closely associated constituents at the cytoplasmic surface of the plasma membrane.