At the onset of both electrically evoked (STIM) and voluntary (VOL) isometric calf exercise there is an increase in vascular conductance of the contralateral lower limb, suggesting withdrawal of muscle sympathetic nerve activity (MSNA). Seven subjects performed STIM or VOL ischaemic calf exercise at 30% maximum voluntary contraction in a seated position. Blood pressure, heart rate and peroneal MSNA in the resting contralateral lower limb were recorded. During both STIM and VOL exercise blood pressure increased (P <0.05). Blood flow increased by 40 +/- 3 and 35 +/- 3% and conductance increased by 37 +/- 3 and 31 +/- 4% (P <0.05) after 10 s of STIM and VOL, respectively, and thereafter declined. The time course and direction of these changes persisted with subjects in a semisupine position, confirming that the transient conductance changes were not an artefact of the dependent leg position. Thigh cuff inflation for 1 min without exercise caused a 47 +/- 7.5% (P <0.05) reduction in MSNA, which recovered when the circulation was restored. However, when cuff inflation was followed by STIM or VOL exercise, MSNA did not fall further. These data suggest that the transient increase in vascular conductance at the onset of contralateral electrically evoked or voluntary lower limb exercise is unrelated to MSNA.