E-cadherin is expressed in both the ZR-75-1-Tx and the ZR-75-1-Ro sublines of ductal breast carcinoma cells and is concentrated at cell-cell borders as shown by immunocytochemical examination. Free cell borders generally show no or little staining. The localized decrease in E-cadherin expression observed after interleukin 6 (IL-6) treatment of either subline correlates with the increase in free cell borders as IL-6 causes cell-cell separation. As we previously reported, many IL-6-treated ZR-75-1-Tx cells round up and detach from the substratum while ZR-75-1-Ro cells remain adherent and display prominent processes. The results are consistent with the view that E-cadherin expression is not responsible for the marked difference in the IL-6-induced phenotypes in these cell lines, although the localized decrease may play a role in cell-cell separation. ZR-75-1-Tx cells are deficient in desmosomes and show a wider intercellular space than ZR-75-1-Ro cells. Alternative mechanisms involving different aspects of the interlinked cytoskeletal and cell adhesion structures are considered to account for the IL-6-induced antimorphogenetic effect.