Dimethyl sulfoxide (DMSO) was administered IV to 6 Thoroughbred horses at 2 dosages: 1.0 g/kg and 0.1 g/kg. The pharmacokinetics seemed linear, with biological half-lives of 8.6 +/- 0.3 hours and 9.8 +/- 2.2 hours for the 1.0 g/kg and 0.1 g/kg dosages, respectively. This was further substantiated by mean residence times of 9.8 +/- 0.44 hours and 13.8 +/- 4.25 hours, areas under the curve of 12.55 +/- 1.42 mg/ml/hr and 1.63 +/- 0.49 mg/ml/hr, and the clearances of 0.081 +/- 0.009 L/kg/hr and 0.066 +/- 0.022 L/kg/hr for the large and small dosages, respectively. At 12 hours after 1.0 g/kg was administered, 26.6% of the DMSO dose was excreted unchanged into the urine; at 12 hours after 0.1 g/kg was administered, 25.3% of the DMSO dose was excreted unchanged into the urine. It was predicted that 29.4% and 40.6% of the total DMSO dose would be excreted into the urine for the 1.0 g/kg and 0.1 g/kg dosages, respectively. A 10% DMSO concentration in normal saline solution was safe to give as rapid IV infusion. Slow administration is recommended for more concentrated solutions. Based on the half-life, DMSO should be administered 2 times a day IV for the treatment of increased intracranial pressure and/or cerebral edema in horses.