The whole-cell recording mode of the patch-clamp technique was used to study the effect of hypotonic NaCl or isotonic high KCl solution on membrane currents in a human osteoblast-like cell line, C1. Both hypotonic NaCl or isotonic high KCl solution activated Cl^- channels expressed in these cells as described before. The reversal potential, E_rev, of the induced Cl^- current is more negative when activated through hypotonic NaCl solution (-47 ± 5 mV; n=6) compared to activation through isotonic high KCl solution (-35 ± 3 mV; n=8). This difference can be explained by an increase in [Cl^-]_i through the activity of a K/Cl cotransporter. K⁺ aspartate was unable to activate the current and furosemide or DIOA suppressed the increase in Cl^- current induced by isotonic high KCl solution. In addition, we used the polymerase chain reaction to demonstrate the presence of KCC1 - KCC4 mRNA in the osteoblast-like cell line. From these results we conclude that human osteoblasts express functional K/Cl cotransporters in their cell membrane which seem to be able to induce the indirect activation of volume-sensitive Cl^- channels by KCl through an increase in the intracellular ion concentration followed by water influx and cell swelling.