In Dictyostelium discoideum, carbohydrate binding proteins (CBPs) or lectins have been implicated in the molecular basis of cellular cohesion. To determine the role of these CBPs, we have attempted to isolate structural gene mutants in which the CBPs have a defective affinity for carbohydrate ligands. We now report the isolation of a spontaneous, cross-reacting material (CRM) mutant which is non-cohesive and fails to develop. The mutant seems to have a defect in the structural gene for one of the two developmentally regulated carbohydrate binding proteins (CBP-26), which renders it unable to bind to galactose-containing ligands. The fact that wild-type cells interact with the mutant and carry it through development strongly supports a model of cell-cell interaction in which cohesion is mediated by complementary molecules.