We have investigated the effects of altered cell shape on the regulation of the 92 kDa type IV collagenase. In MDCK cells, anti-E-cadherin antibodies alter cell shape by disrupting normal cell-cell contacts, while sodium butyrate causes a marked flattening and spreading of cells. The disruption of cell-cell contacts led to a faint expression of the 92 kDa collagenase. This effect was enhanced by sodium butyrate, which by itself did not induce collagenase expression. In contrast, stromelysin expression was not regulated in these conditions. Although mRNA expression was enhanced, the secreted collagenase activity was not altered in these conditions in either cell line. Examination of cytoskeletal and extracellular matrix proteins and cell-cell and cell-matrix adhesion proteins by immunofluorescence and Western blot revealed a disruption of the actin network, tight junctions, and fibronectin deposition by anti E-cadherin antibodies, and alterations in actin, cytokeratin 8, cytokeratin 14, laminin and beta 1 integrin induced by sodium butyrate. Thus, the induction of collagenase expression in epithelial cells by disrupted cell-cell adhesion and sodium butyrate is associated with changes in cell shape and structure.