Studies demonstrate lasting cognitive impairment in elderly persons after anesthesia and surgery. We tested the hypothesis that general anesthesia contributes to this cognitive impairment. Six-and 18-mo-old Fischer 344 rats were trained in a 12-arm radial arm maze and were then randomized to anesthesia for 2 h with 1.2% isoflurane/70% nitrous oxide/30% oxygen or a control treatment consisting of 30% oxygen. Rats recovered for 24 h and then were tested daily on the radial arm maze for 8 wk. Performance of young control rats was stable throughout the experiment. In contrast, aged control rats improved their performance as measured by time to complete the maze but not by error rate. After anesthesia, time to complete the maze did not change in young rats, but error rate decreased (P< 0.05 at 1 and 3 wk), indicating improved performance. In contrast, previously anesthetized aged rats failed to improve with repeated testing and took longer to complete the maze than aged control rats (P< 0.05 at 1 and 3 wk). These data demonstrate that general anesthesia with isoflurane and nitrous oxide improves the memory performance on an established spatial memory task in young rats, but in aged rats it attenuates the improvement in performance that otherwise occurs with repeated testing. Therefore, isoflurane and nitrous oxide anesthesia produces a sustained learning impairment in aged rats.