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Purpose: Effort sense has been suggested to be involved in the hyperventilatory response during intense exercise (IE). However, the mechanism by which effort sense induces an increase in ventilation during IE has not been fully elucidated. The aim of this study was to determine the relationship between effort-mediated ventilatory response and corticospinal excitability of lower limb muscle during IE., Methods: Eight subjects performed 3 min of cycling exercise at 75-85 % of maximum workload twice (IE1st and IE2nd). IE2nd was performed after 60 min of resting recovery following 45 min of submaximal cycling exercise at the workload corresponding to ventilatory threshold. Vastus lateralis muscle response to transcranial magnetic stimulation of the motor cortex (motor evoked potentials, MEPs), effort sense of legs (ESL, Borg 0-10 scale), and ventilatory response were measured during the two IEs., Results: The slope of ventilation (l/min) against CO2 output (l/min) during IE2nd (28.0 ± 5.6) was significantly greater than that (25.1 ± 5.5) during IE1st. Mean ESL during IE was significantly higher in IE2nd (5.25 ± 0.89) than in IE1st (4.67 ± 0.62). Mean MEP (normalized to maximal M-wave) during IE was significantly lower in IE2nd (66 ± 22 %) than in IE1st (77 ± 24 %). The difference in mean ESL between the two IEs was significantly (p < 0.05, r = -0.82) correlated with the difference in mean MEP between the two IEs., Conclusions: The findings suggest that effort-mediated hyperventilatory response to IE may be associated with a decrease in corticospinal excitability of exercising muscle.