Activated Iridium Oxide Film (AIROF) microelectrodes are being proposed for use in multiple neural prosthesis designs because they are characterized by a high charge-delivery capacity. Implicit in their use, is the restriction of limiting the electrode polarization within limits that do not initiate water electrolysis at the electrode/electrolyte interface. These limits, the so-called "water window," are used to ensure that the AIROF electrodes can deliver charge reversibly in various electrolyte environments. Here, we present data from a set of experiments designed to refine the polarization limit criteria used for AIROF electrodes, in vivo. We observe the presence of a secondary ohmic voltage drop that is not seen in vitro. We hypothesize that this secondary ohmic drop may be caused by ion depletion within the AIROF pore structure. The magnitude of this ohmic drop appears to be a function of film thickness, increasing for thicker films. Although increasing the thickness of the AIROF can significantly increase its charge delivery capacity in vitro, the consequence of the thicker film, with respect to deliverable charge, is minimal and can be even detrimental for the in vivo environment. We believe that this phenomenon is mainly due to the ionic inaccessibility of the porous layer structure of the iridium oxide. This study may have widespread consequences for numerous neural prosthesis designs presently being developed, worldwide.