Alterations in activation of pain modulation systems may play a role in the pathophysiology of irritable bowel syndrome (IBS). However, little is known about the effects of exogenous opioids on the perceptual and autonomic responses to aversive visceral stimulation. The aim of the study was to evaluate the effect of the mu opioid-preferring analgesic fentanyl (FEN), given intravenously, on perceptual and autonomic responses to rectal distension. Ten IBS patients and ten normal subjects received, on separate days, either high dose (HD) fentanyl (112 microg bolus followed by 0.04 microg/kg per min infusion), low dose (LD) fentanyl (56 microg bolus followed by 0.02 microg/kg per min) or normal saline (SAL) (50 cc bolus followed by 45 cc/h infusion). Perception thresholds for discomfort and pain during rectal distension were assessed using a tracking paradigm. Intensity and unpleasantness ratings of the distensions, and cardiac autonomic parameters were assessed during randomly delivered rectal stimuli. Effects of FEN on rectal compliance and tone as well as mental status were also assessed. IBS patients had lower perceptual thresholds for discomfort and pain under control conditions. FEN dose-dependently increased the perception thresholds in both healthy control subjects and in IBS patients with a greater relative efficacy in IBS patients than in normal subjects. IBS patients used significantly higher unpleasantness ratings of rectal stimuli compared to healthy controls, but showed no difference in the sensory intensity rating of the stimulus. FEN decreased both intensity and unpleasantness ratings for IBS and normals. FEN lowered cardiosympathetic tone in normal subjects but had no effect on IBS patients. FEN had no effect on rectal tone or compliance. FEN dose-dependently attenuates the perception of phasic rectal distension and affects unpleasantness ratings during random fixed rectal distension, with a greater relative efficacy for this antinociceptive effect in IBS patients. These findings support the hypothesis that IBS patients may have an altered central release of endogenous opioids in response to visceral stimulation.