The effect of fedotozine on visceral hypersensitivity was evaluated in conscious rats. One hour after colonic irritation (0.6% acetic acid intracolonically), a 30 mmHg colonic distension was applied for 10 min. Irritation increased the number of abdominal contractions induced by colonic distension (23.4 +/- 4.1 versus 4.8 +/- 1.4 in saline-treated rats, P < 0.001). Facilitation of colonic pain was reversed in a dose-dependent manner by fedotozine ((+)-(-1R1)-1-phenyl-1-[(3,4,5-trimethoxy)benzyloxymethyl]-N ,N-dimethyl-n-propylamine), (+/-)-U-50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-1-pyrrolidinyl]cyclohexyl)benzen eacetamide) and morphine (respective ED50 values 0.67, 0.51 and 0.23 mg/kg s.c.). The kappa-opioid receptor antagonist, nor-binaltorphimine, abolished the effects of fedotozine and (+/-)-U-50,488H but not those of morphine. Low doses of naloxone (30 microg/kg s.c.) blocked the effect of morphine but not of fedotozine or (+/-)-U-50,488H. After intracerebroventricular administration, morphine was very potent (ED50 1.7 microg/rat), (+/-)-U-50,488H poorly active (58% of antinociception at 300 microg/rat) and fedotozine inactive up to 300 microg/rat. These results show that fedotozine blocks hypersensitive visceral pain by acting on peripheral kappa-opioid receptors in animals.