5-HT-induced acute gastric mucosal injury was assessed in rats by using 5HT(1), 5HT(2), 5HT(3), 5HT(4) or muscarinic receptor related drugs. Rats were treated with antagonists i.p. and 30 minutes later either vehicle, 5-HT (20 mg/kg) or other agonists were administered s.c. The stomachs were removed 4 hours after the last injection and mucosal integrity was assessed by light microscopy using a histological ulcer index (HUI). The HUI was found to be significantly increased following 5-HT administration (1.57 +/- 0.3) when compared with controls (0.14 +/- 0.1). 5HT(1) agonist 5-carboxamidotryptamine (20 mg/kg) produced acute gastric erosion and increased the HUI (P < 0.05). The HUI in the animals receiving 5-HT1D agonist sumatriptan (7 mg/kg) was found to be 1.62 +/- 0.24. 5HT(2) antagonist ketanserine (2.5-15 mg/kg), 5HT(3) antagonist ondansetron (1-5 mg/kg), 5HT(4) antagonist DAU 6285 (1-10 mg/kg) and atropine (1.5-30 mg/kg) exerted no effect whereas 5HT(1/2) antagonist metitepine (0.05-0.5 mg/kg) caused a dose dependent inhibition of the effect of 5-HT. The results from this study demonstrate that 5-HT causes acute gastric mucosal injury and this injury is probably due to the activation of the 5-HT1D receptors.