Abstract The possibility has been investigated that alterations in the plasma membrane interfere with the formation of communicating contacts between cells in vitro. To this end, various rodent cell lines and selected variant strains were simultaneously studied for the composition of membrane-bound carbohydrates and the capacity of forming intercellular communicative junctions. In addition, a variety of somatic cell hybrids of communication-incompetent mouse L cells and several normal, untransformed or neoplastic cells were investigated for the same parameters. Cell-to-cell communication was studied by measuring the cytoplasmic exchange of labelled uridine nucleotides. Maximal intercellular communication was found between cells displaying a normal size-distribution of membrane glycopeptides. In contrast, structural alterations in these molecules, reflected either by altered size-distribution or by a failure to incorporate terminal fucose, were associated with reduced or completely impaired capacity of establishing metabolic cooperation. In somatic cell hybrids complementation by normal genomes suggested the involvement of recessive genetic lesions affecting intercellular communication through disturbances in the genetic control of surface carbohydrate synthesis. The observed correlation between changes in plasma membrane molecules associated with tumour cells and impaired formation of functional cell-cell contacts may reflect a malfunction of tumour cells in their interactions with neighbouring cells or with signal molecules.