Background. The mechanism for pain associated with intravenous administration of propofol is believed to be related to the release of nitric oxide. We hypothesized that pain following propofol injection would be reduced by pretreatment with dexamethasone. Methods. One hundred fourteen female subjects received 5 mL of preservative-free saline, 0.5 mg · kg(-1) of lignocaine hydrochloride 10 mg · mL(-1) or 0.25 mg · kg(-1) of dexamethasone, intravenously, following exsanguination and occlusion of the veins of the arm. This was followed by a 0.5 mg · kg(-1) injection of propofol. Pain scores, facial grimacing, arm withdrawal, and vocalization were recorded prior to and at 15 and 30 seconds following the injection of propofol. Results. The incidence of moderate to severe pain following the injection of propofol was significantly decreased with both lidocaine and dexamethasone. Hand withdrawal was also significantly decreased in comparison to saline. Conclusion. Low dose dexamethasone is commonly used as an antiemetic, and, in larger doses, it has been demonstrated to provide prolonged postoperative analgesia. At higher analgesic doses, dexamethasone may also reduce pain associated with the injection of propofol. This effect is probably related to the effect of the steroid on nitric oxide production associated with intravenous propofol injection.