The purpose of this study was to summarize the clinical findings in 40 dogs with systemic hypersensitivity reactions associated with the administration of potentiated sulfonamides. Dogs ranged from 6 months to 14 years of age, with a mean of 5.7 +/- 3.2 years. Spayed female dogs were overrepresented (24 of 40, or 60% of the dogs), as were Samoyeds (3 of 40; 8%) and Miniature Schnauzers (5 of 40; 13%). Mean dosages of potentiated sulfonamides were 47.0 +/- 14.9 mg/kg/d (range, 23.4-81.4 mg/kg/d). The time from the 1st administration of the drug to the onset of the clinical signs of hypersensitivity ranged from 5 to 36 days, with a mean of 12.1 +/- 5.9 days. There was no relationship between either the dosage or type of sulfonamide given and the time to the onset of the clinical signs. Fever was the most common clinical sign observed (55% of the dogs); thrombocytopenia was 2nd (54%), and hepatopathy (28%) was 3rd. Neutropenia, keratoconjunctivitis sicca (KCS), hemolytic anemia. arthropathy, uveitis, skin and mucocutaneous lesions, proteinuria, facial palsy, suspected meningitis, hypothyroidism, pancreatitis, facial edema, and pneumonitis were also observed in some patients. Of 39 dogs with adequate follow-up, 30 (77%) recovered, whereas 8 (21%) either died or were euthanized, and 1 recovered clinically but had persistent increases in alanine aminotransferase (ALT) activity. Dogs with hepatopathy generally had a poorer prognosis (46% recovery) than dogs without hepatopathy (89% recovery; P = .0035). Sixty-three percent of the dogs with thrombocytopenia recovered, compared to 90% of the dogs without thrombocytopenia (P = .042). Recovery was not associated with sex, age, breed, or type of sulfonamide administered.