1. The whole-cell recording mode of the patch-clamp technique was used to study the effect of extracellular K+ and Rb+ on membrane currents in human osteoblasts, in a human osteoblast-like cell line, and in the Jurkat human leukaemic T cell line. 2. Increasing the extracellular concentration of K+ increased the membrane conductance of the cells in a concentration-dependent manner. This increase in membrane conductance was due to the activation of a Cl- conductance. Rb+ also induced this conductance, but conductance was less than half that seen in K+. 3. The Cl- channel blockers 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and 4-acetamido-4'-isothiocyanatostilbene 2,2'-disulphonic acid (SITS) blocked the K(+)-induced Cl- current in a voltage-dependent manner. The degree of blockade increased with membrane depolarization to a maximum level at 40 mV. At potentials above this value the block appeared to decrease. 4. Both tonicity and K+ were required for maximal activation of the Cl- conductance since the K(+)-induced Cl- conductance could be inhibited by hypertonic solutions and the activation of a volume-sensitive Cl- conductance by hypotonic solutions could be enhanced by extracellular K+. 5. We conclude that an outwardly rectifying Cl- conductance can be activated either upon osmotic swelling or by an increase in extracellular K+. Both activation pathways may be involved in cell volume regulation and seem to apply to volume-sensitive Cl- channels in general since we observe this phenomenon in two different cell types, in human osteoblasts as well as in human leukaemic T lymphocytes.