Subcutaneous administration of granisetron (BRL 43694,endo -1-methyl-N-(9-methyl-9-azabicyclo[3.3.1.]non-3-yl-1H-indazole-3-carboxamide ) and zacopride (4-amino-N-(1-azabicyclo[2.2.2.]oct-3-yl)-5-chloro-2-methoxybenzamide), two 5-HT 3 receptor antagonists, at doses ranging from 3 to 1000 μg/kg, inhibited abdominal contractions induced by distension (30 mmHg, 10 min) of irritated colon (0.6% acetic acid) in conscious rats with a bell-shaped dose-response curve. The ED 5 0 of granisetron and zacopride were 17.6 and 8.2 μg/kg, respectively. In contrast, both tropisetron (ICS 205-930, (3-a-tropanyl)1-indole-3-carboxylic ester) and ondansetron (GR38032F, 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-l-yl)methyl]-4H-carbazo l-4-one hydrocloride dihydrate) were inactive in this model. These data further support the concept of a heterogeneity in the potency of 5-HT 3 receptor antagonists in modulating visceral hypersensitivity in conscious rats. This finding is in agreement with a reported efficacy of granisetron but not of ondansetron in patients with irritable bowel syndrome.