The levels of the gonadal hormones estradiol and progesterone vary throughout the menstrual cycle thereby affecting cognition, emotion, mood, and social behaviour. However, how these hormones modulate the balance of neural excitation and inhibition, which crucially regulate processing and plasticity, is not fully understood. We here used paired-pulse stimulation to investigate in healthy humans the action of low and high estradiol and progesterone on intracortical inhibition in somatosensory (SI) and visual cortex (V1). We found that paired-pulse suppression in both SI and VI depended on estradiol. During high estradiol levels, paired-pulse suppression was significantly reduced. No comparable effects were found for progesterone, presumably due to a confounding effect of estradiol. Also, no hormone level-depending effects were observed for single-pulse evoked SEPs (somatosensory evoked potentials) and VEPs (visual evoked potentials) indicating a specific hormonal action on intracortical processing. The results demonstrate that estradiol globally modulates the balance of excitation and inhibition of SI and VI cortex.