Microelectrodes using activated iridium oxide (AIROF) charge-injection coatings have been pulsed in cat cortex at levels from near-threshold for neural excitation to the reported in vitro electrochemical charge-injection limits of AIROF. The microelectrodes were subjected to continuous biphasic current pulsing, using an 0.4V (versus Ag|AgCl) anodic bias with equal cathodal and anodal pulse widths, for periods up to 7h at a frequency of either 50Hz or 100Hz. At charge densities of 3mC/cm(2), histology revealed iridium-containing deposits in tissue adjacent to the charge-injection sites and scanning electron microscopy of explanted electrodes revealed a thickened and poorly adherent AIROF coating. Microelectrodes pulsed at 2mC/cm(2) or less remained intact, with no histologic evidence of non-biologic deposits in the tissue. AIROF microelectrodes challenged in vitro under the same pulsing conditions responded similarly, with electrodes pulsed at 3mC/cm(2) showing evidence of AIROF delamination after only 100s of pulsing at 100Hz (10,000 pulses total), while electrodes pulsed at 2mC/cm(2) for 7h at 50Hz (1.3 x 10(6) pulses total) showed no evidence of damage. In vitro electrochemical potential transient measurements in buffered physiologic saline indicate that polarizing the AIROF beyond the potential window for electrolysis of water (-0.6 to 0.8V versus Ag|AgCl) results in the observed degradation.