The influence of the menstrual cycle on resting muscle sympathetic nerve activity (MSNA) remains controversial, and the effect of the menstrual cycle on MSNA responses to mental stress is unknown. We examined MSNA, mean arterial pressure (MAP), and heart rate (HR) responses to mental stress (via mental arithmetic) in 11 healthy females during the early follicular (EF) and mid-luteal (ML) phases of the menstrual cycle. The menstrual cycle did not alter resting MSNA (EF, 13 +/- 3 bursts min(-1) versus ML, 13 +/- 2 bursts min(-1)), MAP (EF, 79 +/- 3 mmHg versus ML, 81 +/- 2 mmHg) and HR (EF, 66 +/- 3 beats min(-1) versus ML, 64 +/- 2 beats min(-1)). 5 min of mental stress increased MSNA, MAP and HR during both the EF (delta 4 +/- 2 bursts min(-1), delta 12 +/- 2 mmHg, delta 18 +/- 2 beats min(-1); P < 0.05) and ML (delta 4 +/- 2 bursts min(-1), delta 13 +/- 3 mmHg and delta 20 +/- 2 beats min(-1); P < 0.05) phases. These responses were not different between phases. In contrast, MSNA responses were different between phases during the 10 min recovery from mental stress. MSNA remained elevated during the initial 5 min of recovery in both the EF (delta 6 +/- 1 bursts min(-1); P < 0.01) and ML (delta 7 +/- 1 bursts min(-1); P < 0.01) phases, but only remained elevated during the ML phase (delta 6 +/- 1 bursts min(-1); P < 0.01) during the final 5 min of recovery. Our results demonstrate that MSNA, MAP and HR responses at rest or during mental stress are not different during the EF and ML phases of the menstrual cycle in young, healthy females. However, MSNA activation during recovery from mental stress is prolonged during the ML phase compared to the EF phase.