SummaryPost operative ileus is a serious complication of abdominal surgery in horses and there is evidence that endotoxin plays a significant role in its pathogenesis. Pre‐treatment with intravenous (iv) flunixin (1.1 mg/kg bodyweight [bwt]) or phenylbutazone (4.4 mg/kg bwt) significantly antagonised the acute disruption of gastric, small intestinal and large intestinal motility induced by 0.1 μg/kg bwt iv endotoxin in ponies implanted with gastrointestinal strain gauges. Phenylbutazone was more effective than flunixin and this was significant (P<0.01) for the stomach and left dorsal colon. Both drugs reduced the acute systemic side‐effects of the endotoxin and flunixin was slightly more effective than phenylbutazone in antagonising the cardiovascular effects. These results suggest that the acute effects of endotoxin on bowel motility are mediated at least in part by a cyclooxygenase dependant pathway. Flunixin and phenylbutazone showed a relative selectivity for the cardiovascular and gastrointestinal effects of endotoxin, respectively. Phenylbutazone may be of use clinically in acute colic cases, antagonising the disruptive effects of endotoxin on bowel motility, without entirely blocking the cardiovascular effects which can indicate that the patient has a condition requiring sur