The effects of mental stress (MS) on muscle sympathetic nerve activity (MSNA) and limb blood flows have been studied independently in the arm and leg, but they have not been studied collectively. Furthermore, the cardiovascular implications of postmental stress responses have not been thoroughly addressed. The purpose of the current investigation was to comprehensively examine concurrent neural and vascular responses during and after mental stress in both limbs. In Study 1, MSNA, blood flow (plethysmography), mean arterial pressure (MAP) and heart rate (HR) were measured in both the arm and leg in 12 healthy subjects during and after MS (5 min of mental arithmetic). MS significantly increased MAP (Delta15 +/- 3 mmHg; P < 0.01) and HR (Delta19 +/- 3 beats min(-1); P < 0.01), but did not change MSNA in the arm (14 +/- 3 to 16 +/- 3 bursts min(-1); n = 6) or leg (14 +/- 2 to 15 +/- 2 bursts min(-1); n = 8). MS decreased forearm vascular resistance (FVR) by -27 +/- 7% (P < 0.01; n = 8), while calf vascular resistance (CVR) did not change (-6 +/- 5%; n = 11). FVR returned to baseline during recovery, whereas MSNA significantly increased in the arm (21 +/- 3 bursts min(-1); P < 0.01) and leg (19 +/- 3 bursts min(-1); P < 0.03). In Study 2, forearm and calf blood flows were measured in an additional 10 subjects using Doppler ultrasound. MS decreased FVR (-27 +/- 10%; P < 0.02), but did not change CVR (5 +/- 14%) as in Study 1. These findings demonstrate differential vascular control of the arm and leg during MS that is not associated with muscle sympathetic outflow. Additionally, the robust increase in MSNA during recovery may have acute and chronic cardiovascular implications.