Activation of cultured rat microglial cells by lipopolysaccharide (LPS) induced delayed rectifying outward K+ (I(K)) current. I(K) current was reported to have 'window current', playing a direct role in setting the membrane potential in activated microglia. We used whole-cell patch clamp method to measure the effect of extracellular pH on I(K) current. When pH was changed from 7.4 to 6.4, the activation curve of I(K) current shifted to the right by about 13 mV. Thus, extracellular acidification reduced the window current, resulting in membrane depolarization. These results suggest that extracellular pH regulate the membrane potential in activated microglia.