Dimethyl sulfoxide (DMSO) has shown promise as a drug for the treatment of intracranial hypertension. In this report, we describe our experience in six patients, two who received a bolus administration of 10% DMSO and four who received a 20% solution titrated against the intracranial pressure (ICP). Five of the patients in this series suffered from severe head injury, and one had a cortical venous thrombosis associated with pregnancy. The first two patients were treated with a rapid infusion of a 10% solution of DMSO. Initially, the ICP was satisfactorily controlled using this method. Over time, however, fluid overload, severe electrolyte disturbances, and an ultimate loss of ICP control occurred. In subsequent patients, a 20% solution titrated against the ICP was used. Although ICP control was better achieved using this method of administration, problems with fluid management and electrolytes occurred again despite a high level of vigilance. In addition, because of the solvent properties of DMSO and its propensity over time to dissolve most standard intravenous infusion systems, mechanical difficulties in its administration were encountered in all six patients. The mechanism of action of DMSO is not well understood. It differs from the barbiturates, but acts too rapidly to function solely as a diuretic. The drug is extremely complex to use, and difficulties with its administration may make its risks ultimately greater than its potential benefits. Until more laboratory data are available concerning its use and better delivery systems are developed, neurosurgeons are cautioned against treating intracranial hypertension with DMSO.