Electron transport by the human neutrophil NADPH oxidase is an important microbicidal weapon for phagocytes. The electron current (I-e) generated by the neutrophil NADPH oxidase is poorly characterised due to the lack of appropriate electrophysiological data. In this study, I fully characterise the neutrophil generated I-e when the NADPH oxidase is activated by NADPH and GTP gamma S. The neutrophil I-e was markedly voltage-dependent in the entire voltage range in comparison to those electron currents measured after chloride was removed from the external bath solution. The difference in I-e measured in chloride free conditions was not due to a change in the activation kinetics of voltage-gated proton channels. The I-e depolarises the neutrophil plasma membrane at a rate of 2.3 V s(-1) and this depolarisation was opposed when voltage-gated proton channels are activated. 3 mM ZnCl2 depolarised the membrane potential to +97.8 +/- 2.5 mV (n = 4), and this depolarisation was abolished after NADPH oxidase inhibition. (c) 2008 Elsevier Inc. All rights reserved.