Immune-mediated scouring in sheep is a mucosal hypersensitivity response incited by infective larvae of gastrointestinal nematodes in the southern half of Australia and in New Zealand, regions characterised by a Mediterranean, winter-rainfall climate. To gain insights into the underlying mechanism(s), this study investigated the relationship between nematode infection of sheep in pens, faecal dry matter and release of inflammatory mediators in the intestinal tract. Six worm-free, immune rams received a dose of 3000 Trichostrongylus third stage larvae (L3) and 3000 Ostertagia L3 per week for 6 weeks, after which they were euthanased. Three rams acted as uninfected controls. Faecal dry matter was significantly lower in the infected group from the first week of infection until the end of the trial. Concentrations of cysteinyl leukotrienes and prostaglandin E2 were higher in mucus from both the abomasum and the small intestine of infected rams compared with controls. Within the infected group, concentrations of both mediators were higher in mucus from the small intestine than from the abomasum. There were greater numbers of eosinophilic granulocytes and mucosal mast cells in abomasal and small-intestinal tissue sections from infected rams compared with the controls. The results are consistent with the hypothesis that nematode infection causes an inflammatory response in the gastrointestinal mucosa, characterised by increased fluid secretion.