Propofol causes pain on intravenous injection in 28 to 90% of patients. A number of techniques have been tried to minimize propofol-induced pain, with variable results. In a randomized, double-blind, placebo-controlled trial, we compared the efficacy of ephedrine 30 microg/kg pretreatment to lignocaine 40 mg for prevention of propofol-induced pain. Ninety-three adult patients, ASA 1 and 2, undergoing elective laparoscopic cholecystectomy were randomly assigned to three groups of 31 each. Group 1 received normal saline, group 2 received lignocaine 2% (40 mg) and group 3 received 30 microg/kg ephedrine. All pretreatment drugs were made up to 2 ml. Pain at the time of propofol injection was assessed on a four-point scale: 0=no pain, 1 =mild pain, 2=moderate pain, and 3=severe pain. Twenty-seven patients (87%) of ephedrine pretreatment patients had pain during intravenous injection of propofol as compared to 24 (77%) in the normal saline group. In the lignocaine group, propofol-induced pain was observed in only 13 (42%) when compared with other study groups (P<0.05). Pretreatment with ephedrine 30 microg/kg did not attenuate pain associated with intravenous injection of propofol, nor did it improve haemodynamic stability during induction. However, pretreatment with 2% lignocaine (40 mg) was effective in attenuating propofol-associated pain.