Loss of cell-substratum adhesion is an important factor during tumour progression. We have previously described reduced focal contact components and poorly organized cytoskeletal actin in renal cell carcinomas. In this study, we have used the potent tumour promoter TPA on cultured human renal epithelium to mimic neoplastic transformation. The morphological changes induced by TPA were examined by phase contrast and fluorescence microscopy. TPA treatment caused rounding up of cells and loss of adhesion to either fibronectin or laminin substrata. Cytoskeletal actin was redistributed from orientated stress fibre bundles to a perinuclear circumferential arrangement. This was accompanied by a progressive reduction in the number of vinculin-containing contacts with accumulation of vinculin in punctate spots in the perinuclear region. These altered membrane-cytoskeletal interactions induced by TPA are entirely reversible and mimic epigenetic changes which occur during tumour progression.