We observed, on male athletes, that high blood lactate levels are associated with an enhancement of primary motor cortex (M1) excitability. However, by using the transcranial magnetic stimulation (TMS), gender differences in cortical excitability has been detected. Therefore, in the present study we compare, in young male and female athletes, the effects of high blood lactate levels, induced by performing an exhausting exercise, on the excitability of M1, by using TMS. Subjects were 20 women and 21 men (age: 18-26 ys). Blood lactate levels as well as motor threshold (MT) were measured before, at the end as well as 5 and 10 minutes after the conclusion of the exercise. Subjects performed a maximal exhaustive exercise while motor cortex excitability was evaluated by using TMS; EMG electrodes were placed over the first dorsal interosseus (FDI) muscle. We observed a similar enhancement of M1 excitability, concomitantly with an increase of blood lactate, in both groups of athletes. However, by comparing the intensity of the effect in the two groups, we found a statistically significant difference (P < 0.05) between MT of men (42.0%± 6.43) and women (37.4%± 3.97) 5 min after the conclusion of exercise, i.e. an increase of blood lactate is associated with an greater enhancement of M1 excitability in women with respect to men. This difference could be due, in whole or in part, to the excitatory role of oestrogens on cerebral cortex, probably due to a reduction of GABA levels.