Formation of desmosomal cell-cell contact associated with reorganization of keratin intermediate filaments (KIFs) was observed when cultured cells of a cell line of human skin squamous cell carcinoma were transferred from low (0.07 mM) calcium to high (1.87 mM) calcium medium. At low calcium, cells were dispersed without desmosomal cell-cell contact and the KIFs were mostly concentrated around the nucleus. After 15 min of the transfer, cells contacted each other and formed small colonies and the KIFs initiated to show a radial arrangement. In addition to the cell-cell contact formation and rearrangement of KIFs, the transfer induced fourfold increase of particulate-associated protein kinase C (C-kinase) activity. When 12-O-tetradecanoyl phorbol-13-acetate (PMA), which specifically activates C-kinase, was added to the cells grown at low calcium medium, cell-cell contact formation and radial arrangement of KIF bundles almost identical to those induced by the transfer to high calcium medium were observed. These data suggest a correlation between an increase in C-kinase activity and formation of cell-cell contacts associated with rearrangements of KIFs.