Chloride channels activated by swell have important functions in many physiological processes. The phagocyte NADPH oxidase is essential for host defence and it generates superoxide by transferring electrons from the donor NADPH to the acceptor O-2. This electron current, induces a depolarisation of the plasma membrane. In this study, I report that chloride channels activated by swell can counteract the depolarisation induced by the NADPH oxidase. When a chloride conductance was activated by swelling, its inhibition by either 50 mu M NPPB or removing external chloride, depolarised the plasma membrane potential to +26mV +/- 3.1 (n = 4) and +40 +/- mV (n = 4), respectively. These channels were partially inhibited by the NADPH oxidase inhibitor AEBSF (I mM) and potently inhibited by ZnCl2 (3 mM). These currents were not activated by a phosphorylation step and elevations in intracellular calcium did not appear to activate chloride currents similar to those activated by swell. (c) 2007 Elsevier Inc. All rights reserved.