Thirty-two fit patients scheduled for explorative arthrotomy of the knee were allocated randomly to either halothane/oxygen anesthesia or spinal anesthesia with bupivacaine 0.25 mg · kg−1. The day before and 1, 10, and 21 days after surgery, the aminopyrine breath test (ABT) was performed. The day before and 5, 10, and 21 days after surgery, the antipyrine clearance (APcl) was measured by the single sample saliva technique. The ABT as well as the APclwere increased significantly postoperatively (P< 0.01). The day after surgery the ABT was increased by 13±21% in the spinal anesthesia group only, whereas a late increase by 14±31% was found in the halothane group. Five days after surgery, the APclwas increased by 36±45% in the spinal anesthesia group and by 21±28% in the halothane group. Both tests returned to base line values within 3 weeks postoperatively. In five volunteers following the same sampling scheme but receiving bupivacaine 0.25 mg · kg−1im without surgery, no change in the ABT or the APclwas observed. The authors conclude that surgery may cause microsomal enzyme induction regardless of the anesthetic agent or technique used. The mechanism of this induction remains to be elucidated.