Toxic effects of phenylbutazone (PBZ) [an antiinflammatory agent] in ponies and horses were studied using biochemical, pathophysiologic and pathologic methods. At dosage levels of 10-12 mg/kg body wt per day for 8-10 days, ponies frequently developed clinical signs of toxicosis characterized by hypoproteinemia. Studies using 51CrCl3 demonstrated that PBZ caused a protein-losing gastroenteropathy. Plasma loss was usually associated with gastrointestinal ulceration but sometimes occurred without obvious lesions in mildly affected animals. Similar studies (8.2 mg/kg per day for 13 days) in Thoroughbreds indicated that they were less susceptible to PBZ toxicity; a degree of hypoproteinemia occurred in 4 of 6 treated Thoroughbreds.