Experiments were conducted to assess the effect of chronic stimulation on the electrical properties of the electrode-tissue system, as measured using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Silicon, micromachined probes with multiple iridium oxide stimulating electrodes (400-1600 mu m(2)) were implanted in guinea pig cortex, A 10-17 day post-operative recovery period was followed by five days of monopolar stimulation, two hours/electrode each day using biphasic, constant current stimulation (5-100 mu A, 100 mu s/phase). EIS and CV-data were taken before and after stimulation. The post-stimulation impedance [at mid-range frequencies (100 Hz-100 kHz)] consistently and significantly decreased relative to prestimulation levels. Impedance magnitude increased permanently at low frequencies (<100 Hz), correlating to a change in the charge storage capacity (the area under a cyclic voltammagram). Impedance magnitude significantly increased during the recovery period, though this increase could be mostly reversed by applying small currents, A mathematical model of the electrode-tissue system impedance was used to analyze in vivo behavior, The data and modeling results shows that applying charge to the electrode can consistently reduce the impedance of the electrode-tissue system, Analysis of explanted probes suggests that the interaction between the tissue and electrode is dependent on whether chronic pulses were applied. It is hypothesized that the interface between the tissue and metal is altered by current pulsing, resulting in a temporary impedance shift.