Dimethylsulfoxide (DMSO) is a common vehicle used for many drugs used in neuroprotective experiments. DMSO has many biological effects, including antiinflammatory, antioxidant, and local anesthetic effects that could be neuroprotective. To determine if DMSO is neuroprotective in ischemia, DMSO (0, 0.01, 0.03, 0.1, 0.3 and 1.0 ml) was administered intraperitoneally 30 min prior to permanent middle cerebral artery (MCA) occlusion in the rat. Twenty-four hours after MCA occlusion, brains were removed and sectioned. Mean infarction volume was significantly reduced in rats treated with 0.1, 0.3 and 1.0 ml of DMSO compared to saline controls. There was no acute effect of drug treatment upon arterial blood gasses or mean blood pressure. These results suggest that DMSO is neuroprotective in focal cerebral ischemia. Investigators must use appropriate controls when DMSO is used as a vehicle. (C) 1997 Elsevier Science Ireland Ltd.