The pulse-clamp method was applied in order to confirm that a significant amount of oxygen is electrochemically reduced on the time scale of a typical neurostimulation pulse (100 mus). Studies were conducted on gold wire electrodes in 1M NaCl phosphate buffer solution at pH 7.4 and in atmospheres of 100% nitrogen or 100% oxygen. Results of slow cyclic voltammetry in this system indicate that during quasi-steady-state conditions, oxygen was reduced by a two-electron pathway. Using the pulse-clamp method developed by Bonner and colleagues, we were able to show that significant oxygen reduction also occurred during typical neural stimulation pulses and that the process was irreversible. The increase m unrecoverable charge that was associated with oxygen reduction occurred at charge densities as low as -10 muC/cm2 and potentials of -0.30 V SCE in oxygen-containing systems. Hydrogen evolution did not occur until the charge density exceeded -75 muC/cm2 and potentials exceeded -1.20 V SCE. Pulse width and delay experiments indicate that wider pulses and longer delays between the cathodic and anodic phases resulted in a greater fraction of the unrecovered charge attributed to oxygen reduction. Results also suggest that once hydrogen evolution began, the unrecovered charge associated with oxygen reduction was markedly reduced. The occurrence of significant oxygen reduction during stimulation can result in the formation of highly reactive radical species that are known to be damaging to cell membranes, proteins, and DNA. These species could play a role in the tissue damage that is seen during neural stimulation.