This report concerns the expression of the gap-junction proteins Connexin (Cx)26, 32 and 43 in different malignant and non-malignant human tissues. Affinity-purified polyclonal antibodies against Cx26, 32 and 43 were used for immunohistochemical as well as immunoblot analysis. Cx32, the major gap-junction protein in rat and mouse liver, was detected in human liver and kidney. By contrast, Cx43 was expressed in epithelial and mesenchymal tissues and Cx26 was detected in different epithelia. Whereas all of the benign tumors studied, and some malignant ones, showed stable expression of gap-junction proteins, breast cancer, renal-cell cancer and sarcomas showed a significant decrease in gap-junction proteins as opposed to normal tissue. Cx43, not detected in human normal liver, was found in human hepatocellular carcinoma and Cx26, not detected in human adult skin, was observed in tissue samples of basal-cell carcinoma. In immunoblot analysis, Cx32 antibodies recognized a 27-kDa protein in human liver and hepatocellular carcinoma. A 43-kDa polypeptide was detected in human kidney, renal-cell carcinoma, normal breast, connective tissue of invasive-duct carcinoma of the breast and hepatocellular carcinoma.