The dose response of the nonsteroidal anti-inflammatory drug, ibuprofen, was evaluated in order to determine the most efficacious dose in the treatment of canine endotoxin shock. Fifteen minutes after an infusion of Escherichia coli endotoxin, four groups of dogs were given a single iv dose of 1, 5, 10, or 20 mg/kg of ibuprofen. These groups were compared to endotoxin only and saline control groups. All ibuprofen doses significantly improved the systolic, diastolic, and mean systemic arterial BP. The improvement in systemic BP was accompanied by an increase in the systemic vascular resistance. Pulmonary vascular pressures and resistance also increased after ibuprofen administration. The lack of a dose response and the demonstrated beneficial effect of low dose ibuprofen in the reversal of the hypotension associated with experimental canine endotoxin shock lead us to recommend the use of low dose ibuprofen for future endotoxin and sepsis studies. Use of low dose ibuprofen might have less of an effect on renal perfusion and would therefore be more likely to produce the beneficial hemodynamic response without compromising renal function.