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Simultaneous administration of a nonselective COX inhibitor and a COX-2 specific NSAID has not been previously reported in horses. The goal of this study was to determine the safety of a 10-day dosage regimen of phenylbutazone and firocoxib, both at their standard dosages, in horses. Six horses were administered 2.2 mg/kg of phenylbutazone and 0.1 mg/kg of firocoxib by mouth, daily for 10 days. Horses were assessed daily for changes in behavior, appetite, fecal consistency, signs of abdominal pain, and oral mucous membrane ulceration. Horses were assessed prior to and on the last day of treatment for changes in serum creatinine, albumin, total protein, and urine-specific gravity. Horses underwent endoscopic examination of the esophagus, stomach, and pylorus prior to and 24 hours after the last treatment. A significant change in serum creatinine and total protein was observed on day 10 of treatment. No other significant findings were noted during the experiment. Results indicated that co-administration of phenylbutazone and firocoxib may cause renal disease.