Previously we have used immunocytochemistry to identify A-CAM as a major cell adhesion molecule in human renal tubular epithelium. In this study, we demonstrate the calcium dependence of cell-cell adhesion and A-CAM function in cultured human renal epithelial cells. Separation of adjacent cells was seen within 1 min following sequestration of calcium from the culture medium with EDTA. This loss of intracellular adhesion in low calcium conditions was accompanied by the disappearance of A-CAM immunoreactivity. The changes were reversible and on return to normal calcium concentrations, A-CAM immunoreactivity reappeared and cell adhesion was re-established. The time course of this recovery was slow, taking 2-3 h. These results demonstrate the calcium dependence of cell adhesion in cultured human renal epithelial cells and confirm the adhesive function of the immunoreactive A-CAM molecule.