BACKGROUND Pain on injection of propofol in children has been reported to be as high as 30-80%. The reason for the pain is assumed to be the aqueous phase of the propofol emulsion. Therefore, for the first time, this study tested the hypothesis that dilution of propofol to a 0.5% emulsion might reduce the incidence of pain during propofol injection. METHODS The study design was prospective, monocenter, double-blind, and randomized. Sixty-four children aged 2-6 yr were scheduled to receive 0.5% or 1.0% propofol in a medium-chain-triglyceride/long-chain-triglyceride emulsion. Incidence and intensity of pain were assessed by spontaneous expressions of pain and withdrawal of the arm. In a subgroup of 21 children, serum triglyceride levels were measured before and 3 and 20 min after induction. Adverse events were recorded. RESULTS Amounts of propofol required until loss of eyelash reflex were 4.40+/-1.01 mg/kg for 0.5% propofol and 4.31+/-0.86 mg/kg for 1.0% propofol. Percentages of children who showed at least one pain reaction were 23.3% in the 0.5% propofol group and 70.0% in the 1.0% propofol group (P<0.001). Serum triglycerides were higher in the 0.5% propofol group 3 and 20 min after injection (251.7 vs. 148.8 mg/dl; P=0.001 and 135.5 vs. 75.5 mg/dl; P=0.03). Adverse events or complications did not occur. CONCLUSIONS Dilution of propofol to a 0.5% medium-chain-triglyceride/long-chain-triglyceride emulsion reduced pain effectively during injection in children aged 2-6 yr. Cumulative doses until 4-5 mg/kg propofol led to moderate increases of triglyceride levels and did not result in significant adverse events.