We studied the effect of propofol, a widely used sedative-hypnotic drug, on pain perception. Eighteen subjects received propofol in two sedative concentrations that were balanced and randomized in order. Painful (45 degrees C, 47 degrees C, and 49 degrees C) stimulation temperatures were presented in random order, and nonpainful 31 degrees C stimuli were presented on alternate trials. We used a target-controlled infusion and chose effect site concentrations of 0.5 mug/mL for mild sedation and 1.0 mug/mL for moderate sedation. Using a visual analog scale, subjects rated both pain intensity and unpleasantness higher when sedated with propofol. The average pain intensity was 28/100 for placebo, 35/100 for mild, and 40/100 for moderate sedation. Pain unpleasantness was 23/100 for placebo, 29/100 for mild, and 33/100 for moderate sedation. This effect was unexpected and may be explained by a difference of subjective pain experience by a patient and the perceived level of analgesia by a health care provider in sedated patients. This finding calls further attention to the need for adequate analgesia in patients sedated with propofol.