Animal experiments show that motor recovery after focal brain injury is accelerated by the indirect norepinephrine agonist methylphenidate (MPH). The underlying mechanisms are unknown, but an MPH-induced increase in cortical excitability has been advocated. Here, we tested the acute effects of a single oral dose of 40 mg MPH (Ritalin) on motor cortical excitability in eight healthy subjects using focal transcranial magnetic stimulation. MPH increased the slope of the motor evoked potentials (MEP) intensity curve in a hand muscle, reduced short-interval intracortical inhibition, and increased I-wave facilitation. MEP threshold, cortical silent period and measures of spinal and neuromuscular excitability remained unaffected. Findings support the idea that MPH promotes accelerated motor recovery after lesion through facilitation and disinhibition.