The effects of pharmacological modulation of adrenergic receptors on colonic motor and sensory function are unclear. We studied 40 healthy volunteers in a single-blind design; 12 received saline, and the remaining 28 received either clonidine, yohimbine, phenylephrine, or ritodrine. A barostat-manometric assembly in the left colon recorded drug effects on fasting and postprandial motor function, compliance, and sensation in response to standardized phasic balloon distensions delivered in random order. Clonidine reduced and yohimbine increased fasting, but not postprandial tone, by 63.2 +/- 22.3% and 24.8 +/- 8.8% (SE), respectively. Clonidine tended to reduce fasting phasic activity in the descending and sigmoid colon. A power exponential model provided the best fit to the compliance curve. Clonidine significantly increased colonic compliance. Clonidine reduced and yohimbine increased colonic perception of pain but not gas sensation during distension. Phenylephrine and ritodrine did not influence colonic motor or sensory function in the present studies. Thus alpha 2-receptors modulate fasting colonic tone and compliance and alter perception of pain but not gas during mechanical stimulation of the colon.