OBJECTIVE Potential drugs for human acute renal failure are often tested in an animal model of renal ischemia/reperfusion injury. Analgesics are often not given after surgery because of concerns that they would alter renal function. Therefore, we tested whether postoperative analgesia would alter animal health or affect the degree of renal injury. METHODS Mice were subjected to either 32 or 37 minutes of renal ischemia, given two or six doses of buprenorphine or vehicle at 12-hour intervals, and followed for 72 hours. In some animals, we measured body temperature and physical activity by use of telemetry. RESULTS Animals treated with buprenorphine recovered more rapidly from surgery based on postoperative activity, and had a small but not significant tendency for faster restoration of normal body temperature. Animals treated with buprenorphine had less weight loss after 37 minutes of ischemia. Buprenorphine given after surgery did not influence the degree of renal injury after ischemia/reperfusion. CONCLUSIONS Buprenorphine should be given after renal ischemia-reperfusion surgery because administration of the proper analgesic improved animal health without interfering with the renal ischemia/reperfusion model. Analgesic treatment at the time of the operation and 12 hours after was sufficient. Buprenorphine may reduce the post-surgical stress response, and thus potentially improve the specificity of testing for drugs that reduce or treat renal injury.