Bone cells share common responses to external stimuli with most other cells. Among these are changes in membrane ion channel activity, although at present, relatively little is known about their nature or significance in human bone cells. Using the whole-cell configuration of the patch-clamp technique, we have revealed two types of membrane current in MG63 human osteoblast-like cells. With a potassium-based dialysis solution and a holding potential of -40 mV, voltage commands to more negative potentials elicited an inward current. This current showed little inactivation with time during the command pulse and exhibited some characteristics of an inwardly rectifying K current, including sensitivity to external K and Ba. The second type of current was outward, activated by depolarizing pulses from -40 mV. This current was transient in nature, activating in the first 50 ms of the pulse and then showing rapid inactivation to reach a steady-state level after 4 to 5 seconds. The transient outward current was sensitive to block by TEA, CTX, and to a lesser extent, Ba. These data suggest that a large proportion of this outward current is carried by K ions through channels that may be sensitive to the internal Ca ion concentration. The transient outward current was enhanced by setting the holding potential at -100 mV, and greatly inactivated by setting it at 0 mV. Increased understanding of the significance of these membrane currents may allow development and use of agents to modulate their action and therefore influence bone cell behavior in disease states such as osteoporosis.