OBJECTIVE To determine the potential efficacy of intravenous (IV) infusion of pentoxifylline (PTX) before nephrolithotomy on attenuating plasma level of the tumor necrosis factor (TNF)-alpha and interleukin (IL)-1, and to investigate whether it prevents postoperative pain. METHODS In a randomized, double-blind, placebo-controlled study, 32 patients (American Society of Anesthesiologists physical status 1 and 2) who were undergoing general anesthesia for nephrolithotomy were randomized to receive intravenous PTX (500 mg in 500 mL saline for 2 hours followed by 700 mg in 1000 mL saline for 6 hours), or placebo (1500 mL saline) before induction of the anesthesia. Two venous blood samples were obtained 10 minutes before PTX or placebo infusion and after surgery at 24 hours for laboratory examination. After surgery, the amount of narcotics consumption and intensity of pain (Visual Analog Scale and Verbal Rating Scale) were evaluated. RESULTS At baseline, both placebo and PTX group had similar demographic, clinical, and laboratory characteristics. The use of narcotic analgesia (morphine, pethidine or both) was more common in the control group for pain relief. Also, pain intensity was significantly lower in patients who received PTX in comparison with those in the control group. Patients in the PTX group had lower postoperative plasma levels of TNF-alpha (0.27 pg/mL (0.06/0.74) v 3.35 pg/mL (0.83/6.41)) (median (25%/75%), P < 0.0001) and IL-6 (35.4 +/- 21.1 pg/mL (range 12-100) v 60.4 +/- 16.7 pg/mL (range 38-100), mean +/- standard deviation, P < 0.001) compared with the placebo receivers. There was no significant difference in surgery time, length of hospital stay, and fever occurrence after operation during in-hospital follow-up. Nausea and vomiting developed, however, in 5 (31.2%) of treatment patients. CONCLUSIONS An infusion of IV PTX that is administered preoperatively could be applied to reduce inflammatory changes and pain intensity in patients undergoing nephrolithotomy; it causes no serious side effects.