Postinfectious irritable bowel syndrome may develop subsequent to acute bacterial enteritis. We therefore hypothesized that intestinal afferents may develop hypersensitivity upon exposure to luminal lipopolysaccharide (LPS) from pathogens but not from commensal bacteria and that this may be prostaglandin mediated. Extracellular recordings of jejunal afferents were obtained in vivo from male Wistar rats (n = 5 per group; 300-400 g). Lipopolysaccharide from Escherichia coli (E-LPS), Salmonella typhimurium (S-LPS) or vehicle were infused into the intestinal lumen at 5 mg mL(-1). The selective 5-HT(3)-receptor agonist 2-methyl-5-HT (2m5-HT, 15 microgkg(-1), i.v.) was administered at 15-min intervals before and up to 2 h after S-LPS administration. Intraluminal E-LPS had no effect on mesenteric afferent nerve discharge at baseline. By contrast, afferent discharge increased from 21.7 +/- 0.3 impsec(-1) to 28.8 +/- 3.4 impsec(-1) 40 min after S-LPS administration (mean +/- SEM; P < 0.05) and reached 38.8 +/- 4.1 impsec(-1) after 2 h (P < 0.05). The afferent response to 2m5-HT was enhanced 30 min following S-LPS by 30.9 +/- 3.9% (P < 0.05) and remained elevated thereafter. The increase in baseline discharge and sensitivity to 2m5-HT following S-LPS was prevented by pretreatment with naproxen (COX inhibitor, 10 mgkg(-1) i.v.) or AH-6809 (EP1/EP2 receptor antagonist, 1 mg kg(-1)). Intestinal afferents do not alter their discharge rate to LPS from E. coli but to LPS from the pathogenic bacterium S. typhimurium. The latter response entails afferent sensitisation to 2m5-HT that depends on prostanoid release. This acute sensitisation may prime the intestinal afferent innervation for a later development of persistent hypersensitivity.