Binding of Ricinus communis I agglutinin to the outer surface of resealed human erythrocyte ghosts results in an organizational perturbation that is translated to the inner membrane surface. The organizational change was detected by an enhancement in the chemical cross-linking of several erythrocyte membrane components by the bifunctional reagent, dimethyl malonimidate, resulting in their loss or reduction after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the solubilized erythrocyte components. Of the components that failed to appear, or are reduced in amount, on the gels (protein bands Ia, Ib, IVa, and VII), two are known to be the subunits of spectrin (bands Ia and Ib), an inner-surface peripheral protein. A new band, which was identified as R. communis lectin, appeared on the polyacrylamide gels of lectin-treated ghosts with or without crosslinking. The loss of spectrin and other bands after lectin treatment and chemical crosslinking was due to a specific transmembrane event because: (a) beta-lactose, an inhibitor of R. communis agglutinin, prevented labeling of ghosts by the lectin and loss of spectrin and other erythrocyte components on gels after crosslinking; (b) use of inactive bifunctional or active monofunctional crosslinking reagents did not result in loss of spectrin or other components from lectin-treated ghosts; (c) the loss of spectrin and other components after lectin treatment and crosslinking was sensitive to temperature and lectin concentration; (d) no new bands appeared on the gels except for the band identified as R. communis agglutinin; (e) R. communis agglutinin does not interact with purified spectrin; and (f) previously published data indicate the R. communis lectin binds exclusively to the outer membrane surface while spectrin is located on the inner membrane surface. Perturbation of components of the outer membrane surface that can be translated to the cell interior by transmembrane linkages may provide a structural means of membrane communication that could be important in a variety of cellular control processes.