A randomized, placebo-controlled, double-blind study was performed as a pilot study to examine the benefit of the administration of magnesium sulfate given intravenously as a protective substance during the first 24 hours following a stroke. Patients who had cortical infarction in the middle cerebral artery territory with moderate to severe neurologic deficits lasting for more than 15 minutes with onset less than 24 hours were included. The patients were treated with magnesium sulfate or placebo for 5 days and examined by a blinded investigator. Patients had follow-up for 30 days. The primary efficacy variable was the proportion of patients reaching mild to moderate neurologic deficit on the Orgogozo scale (80 points) and relative functional independence on the Barthel index (60 points). Orgogozo scale and Mathew scale values were obtained on admission and days 2, 4, 8, and 30 after stroke. Barthel activities of daily living index and Rankin disability score were obtained on day 30. Forty-one patients (22 given treatment and 19 given placebo) demonstrated significant beneficial effects on the Orgogozo scale (84 +/- 11 vs. 64 +/- 10, p < 0.0001) and (83 +/- 14 vs. 70 +/- 15, p < 0.009), respectively. At the end of 1-month follow-up, the Barthel ADL index was nonsignificantly higher and the Rankin disability score was marginally significantly lower in the magnesium-treated group (84 +/- 26 vs. 71.8 +/- 26, p < 0.143) than in control subjects (2.3 +/- 1.1 vs. 3 +/- 1.3, p < 0.077). Intravenous magnesium sulfate had significant positive effect on the outcome in patients with acute stroke. Further studies on a larger scale are needed to confirm these findings.