OBJECTIVE Selegiline (L-deprenyl) is a selective monoamine oxidase B (MAO-B) inhibitor used in the treatment of Parkinson's disease. In addition, it is thought to rescue neurons with a loss of target-derived trophic support. Several mechanisms have been proposed to explain these phenomena, such as the production of neurotrophic actions through astrocyte activation, reduction of free radical production, or the presence of antiapoptotic properties. The aim of this study was to investigate whether the systemic administration of selegiline facilitates recovery after a cerebral infarction in humans. METHODS This phase II study was randomized, double-blind, and placebo controlled. Selegiline, 5 mg, or matched placebo was given twice a day for 3 months. The drug therapy was started within 48 h after a hemispheric infarction in the territory of middle cerebral artery. There were 24 patients recruited. Twenty patients were followed up to 3 months or until their death, and they represent the efficacy analysis group. The primary efficacy parameters were Scandinavian Stroke Scale (SSS), Barthel Index (BI), and Fugl-Meyer Scale (FMS). Secondary parameters were Zung Self-Rating Depression Scale (ZDS) and 15-Dimensional Measure of Health Related Quality of Life test (15-D). RESULTS SSS improved statistically significantly from the baseline when compared with placebo (p = 0.019). The results were parallel among the other two primary efficacy variables (BI and FMS), showing a positive trend for selegiline, although they did not reach statistical significance. Similarly, in the analysis of the secondary efficacy variables, both the 15-D test and ZDS supported this positive trend in favor of selegiline, although no statistically significant differences between groups were found (p = 0.06 in 15-D test). CONCLUSIONS Selegiline seems to be beneficial after a cerebral infarction. This benefit may be due to the enhancement of the recovery process.