Direct currents (DC) applied directly to central nervous system structures produce substantial and long-lasting effects in animal experiments. We tested the functional effects of very weak scalp DC (< 0.5 mA, 7 s) on the human motor cortex by assessing the changes in motor potentials evoked by transcranial magnetic brain stimulation. We performed four different experiments in 15 healthy volunteers. Our findings led to the conclusion that such weak (< 0.5 mA) anodal scalp DC, alternated with a cathodal DC, significantly depresses the excitability of the human motor cortex, providing evidence that a small electric field crosses the skull and influences the brain. A possible mechanism of action of scalp DC is the hyperpolarization of the superficial excitatory interneurones in the human motor cortex.