Abstract Objective—To determine the pharmacokinetics of acetazolamide administered IV and orally to horses. Animals—6 clinically normal adult horses. Procedure—Horses received 2 doses of acetazolamide (4 mg/kg of body weight, IV; 8 mg/kg, PO), and blood samples were collected at regular intervals before and after administration. Samples were assayed for acetazolamide concentration by high-performance liquid chromatography, and concentrationtime data were analyzed. Results—After IV administration of acetazolamide, data analysis revealed a median mean residence time of 1.71 ± 0.90 hours and median total body clearance of 263 ± 38 ml/kg/h. Median steady-state volume of distribution was 433 ± 218 ml/kg. After oral administration, mean peak plasma concentration was 1.90 ± 1.09 µg/ml. Mean time to peak plasma concentration was 1.61 ± 1.24 hours. Median oral bioavailability was 25 ± 6%. Conclusions and Clinical Relevance—Oral pharmacokinetic disposition of acetazolamide in horses was characterized by rapid absorption, low bioavailability, and slower elimination than observed initially after IV administration. Pharmacokinetic data generated by this study should facilitate estimation of appropriate dosages for acetazolamide use in horses with hyperkalemic periodic paralysis. (Am J Vet Res 2000;61:965–968)