Recent clinical studies emphasize the importance of early (less than 12 hours after onset) treatment of patients with acute ischemic stroke. Therapies have been proposed as being effective because of early clinical improvement. The frequency and degree of spontaneous improvement in such patients, however, is unknown. We prospectively evaluated the course of 29 patients (19 men, 10 women) aged 33-82 years who were seen less than or equal to 12 hours after the onset of acute ischemic stroke. Seventeen patients were first evaluated less than or equal to 6 hours and the remaining patients at 6-12 hours after onset. All patients were examined using a modified National Institutes of Health Stroke Scale at baseline, 1, 2, 3, and 6 hours. No specific treatment for acute ischemic stroke was given during this time. Improvement (defined as a decrease of greater than or equal to 2 points from baseline score) was noted at 1 hour in seven patients (24%). By 6 hours 15 patients (52%) had improved, 12 (41%) were unchanged, and two (7%) were worse. Our results suggest that spontaneous, often dramatic improvement occurs in patients with acute ischemic stroke and should be taken into consideration in the design of any trial of acute treatment.