Membrane currents of cultured human monocytes and rat microglia were recorded with the whole-cell patch clamp technique. Freshly isolated monocytes or resting (proliferating) microglia express only inwardly rectifying K+ channels. However, incubation in teflon bags leads to the expression of additional, outwardly rectifying K+ channels. The outward K+ conductance of microglial cells was inhibited by intracellular Cs+ and extracellular 4-aminopyridine or tetraethylammonium. Functional similarities with the microglial outwardly rectifying K+ channel were found in the Kn-channel of lymphocytes which has recently been cloned (RGK5). The polymerase chain reaction (PCR) was used to demonstrate the presence of RGK5-like mRNA in microglia.