The effect of ketamine alone and in combination with N2O (70% inspired) on median nerve somatosensory evoked potentials (SSEPs) was investigated in 16 neurologically normal patients undergoing elective abdominopelvic procedures. The anesthetic regimen consisted of ketamine (2 mg/kg iv bolus followed by continuous infusion at a rate of 30 μg·kg−1·hr−1), neuromuscular blockade (atracurium), and mechanical ventilation with 100% oxygen. SSEP recordings were obtained immediately preinduction and at 2, 5, 10, 15, 20, and 30 min postinduction. Thereafter, N2O was added with surgical incision and maintained for 15 min. At 5-min intervals, SSEP recordings were again taken during and after N2O. With minor exceptions, mean cortical and noncortical latencies as well as noncortical-evoked potential amplitude were unaffected by either ketamine or N2O. Ketamine induction increased cortical amplitude significantly with maximal increases occurring within 2–10 min. For example, at 5-min postinduction, mean N1-P1 amplitude increased from 2.58 ± 1.05 (baseline) to 2.98 ± 1.20 μV and P1-N2 amplitude increased from 2.12 ± 1.50 (baseline) to 3.99 ± 1.76 μV. Throughout the 30-min period after ketamine induction, mean P1-N2 amplitude increased generally by more (57–88%) than did mean N1-P1 amplitude (6–16%). N2O added to the background ketamine anesthetic produced a rapid and consistent reduction in both N1-P1 and P1-N2 amplitude. Thus, at 1 min after N2O, mean N1-P1 amplitude decreased from 2.74 ± 1.11 to 1.64 ± 0.63 μV, while P1-N2 amplitude decreased from 3.32 ± 1.52 to 1.84 ± 0.87 μV. After 15 min of N2O, these amplitudes remained depressed at 1.35 ± 0.52 and 1.72 ± 0.71 μV, respectively. On elimination of N2O level. It is concluded that, when used as the sole anesthetic agent, ketamine enhances the cortical component of the human somatosensory evoked potential. However, when N2O is introduced, the ketamine enhanced cortical amplitude is reduced by approximately 50%. When judged against the known depressant effect of N2O, this would suggest that ketamine and N2O are near additive with respect to their effects on cortical SSEP amplitude.