Human erythrocytes specifically bind 125I-insulin in a manner similar to cells in which insulin exerts a physiological response. In addition, erythrocytes are of practical value for correlating in vitro insulin binding with in vivo carbohydrate intolerance. The competitive binding of labelled and unlabelled insulin to erythrocyte receptor3 is typically curvilinear when plotted according to Scatchard. The curvilinear nature of the Scatchard plot describing insulin binding to membrane receptors, although originally attributed to heterogeneous sites, has been more recently interpreted as negative cooperativity between homogenous sites. Evidence reported here, however, suggests that there are two populations of insulin receptors on erythrocytes. Specific concentrations of concanavalin A (Con A), a lectin which mimics insulin activity, are shown here to inhibit one population of receptors leaving another population unaffected.