With an assay that quantitates the transfer of 6-thioguanylic acid from hypoxanthine phosphoribosyltransferase (IMP:pyrophosphate phosphoribosyltransferase, EC 18.104.22.168)-positive donor cells to negative recipient cells through gap junctions, differences in contact-mediated communication between normal and transformed human cells in culture have been detected. We have compared cells cultured from human tumors and simian virus 40-transformed cells with the normal human fibroblasts from which they were derived as well as with gap junction-deficient L cells. The communication, which is extensive in normal cells, is significantly reduced when transformed cells are used as either donors or recipients in the contact-feeding assay. Furthermore, the reduction in the transfer of nucleotides is enhanced when transformed cells are used as both donors and recipients, indicating a dosage effect or synergism, independent of enzyme activity. Fetal cells have a contact-feeding phenotype intermediate between that of normal and that of transformed cells. We suggest that the decrease in communication of nucleotides in transformed cells reflects quantitative or qualitative changes in membrane components responsible for gap junction formation.