Macroscopic and microscopic currents have been recorded using human microglia isolated from fetal human brains (12-20 weeks gestation). Within a period of two days following plating of cells, inward K+ currents were small (mean amplitude of 0.3 nA at -100 mV) and outward K+ currents were not observed. For periods in excess of five days after adherence to substrate, an inactivating outward K+ current, sensitive to 4-aminopyridine, was expressed. A slowly rising current, blocked by tetraethylammonium, was also evident in a small population of human microglia. This current was activated with cell depolarization positive to +10 mV and had properties similar to those recently described for a proton current in mouse cells. In early adherent cells (days 1 or 2 after plating), treatment of microglia with interferon-gamma led to the expression of outward K+ current which was lacking in the absence of the treatment. In excised, inside-out patches, two high conductance channels were identified. A calcium-dependent K+ channel (unitary conductance of 106 pS with physiological levels of K+ across the patch) had an open probability of 0.5 with internal Ca2+ at 7 microM and the patch potential at 0 mV. In addition, an anion channel (unitary conductance of 280 pS) was transiently activated with depolarizing or hyperpolarizing steps applied from 0 mV. Characterization of the macroscopic and unitary properties of currents in microglia will have relevance to a description of putative cell functions in the human CNS. In particular, modification of cell electrophysiological properties by various activating stimuli may contribute to signalling processes in CNS pathology.