The effect of cisapride pretreatment on gastric emptying in horses was determined by measuring serum concentrations of acetaminophen, a drug known to be readily absorbed in the small intestine but not in the stomach. The time to reach maximum serum acetaminophen concentrations (Tmax), the maximum serum concentrations (Cmax) and the area under the serum acetaminophen concentration vs. time curves (AUC) were compared among treatment groups. In the first part of the study, the effect of orally administered cisapride (0.1, 0.2 and 0.4 mg/kg bwt) on gastric emptying was examined in 6 normal fasted horses. In the second part of the study, gastric emptying in horses given endotoxin i.v. (n = 6) was compared to those that received cisapride per os prior to administration of endotoxin (n = 6) and those that received neither compound (n = 6). Cisapride did not alter gastric emptying in normal horses. Endotoxin caused a profound delay in gastric emptying and pretreatment with cisapride significantly attenuated this effect. It is concluded that cisapride may be useful as a prophylactic measure when administered prior to the development of endotoxaemia.