Knowledge of the natural history of certain stroke subtypes is essential for the proper analysis and interpretation of clinical trials of stroke therapy. We evaluated the degree of weakness on admission and again 7 to 10 days later in 62 patients with pure motor hemiparesis (PMH) and 280 patients with motor deficits from other stroke syndromes (OSS). During the 7-to-10-day study interval, we found that the OSS group worsened slightly in motor function, whereas the PMH group improved (p = 0.01). Among those who improved in both groups, those in the PMH group improved to a greater extent than did those in the OSS group (p = 0.02). This occurred despite a greater frequency of worsening during the first 12 hours after stroke onset in the PMH group. By the fourth day following PMH onset, a majority of patients had improved, and this improvement was sustained until day 10. The two groups did not differ significantly in age, race, sex, history of cardiac disease, hematocrit, anticoagulation treatment, blood glucose, or medical complications in hospital. Lacunar infarcts occurred in 84% of PMH and 23% of OSS. Patients with PMH show significant spontaneous improvement in weakness within 7 to 10 days of admission, compared with patients with OSS. Stratification by admission stroke syndrome in clinical trials may be necessary before judging the efficacy, or lack thereof, of a therapeutic agent.