Increases in sympathetic neural activity occur independently with either vestibular or mental stimulation, but it is unknown whether sympathetic activation is additive or inhibitive when both stressors are combined. The purpose of the present study was to investigate the combined effects of vestibular and mental stimulation on sympathetic neural activation and arterial pressure in humans. Muscle sympathetic nerve activity (MSNA), arterial pressure, and heart rate were recorded in 10 healthy volunteers in the prone position during 1) head-down rotation (HDR), 2) mental stress (MS; using arithmetic), and 3) combined HDR and MS. HDR significantly (P < 0.05) increased MSNA (9 +/- 2 to 13 +/- 2 bursts/min). MS significantly increased MSNA (8 +/- 2 to 13 +/- 2 bursts/min) and mean arterial pressure (87 +/- 2 to 101 +/- 2 mmHg). Combined HDR and MS significantly increased MSNA (9 +/- 1 to 16 +/- 2 bursts/min) and mean arterial pressure (89 +/- 2 to 100 +/- 3 mmHg). Increases in MSNA (7 +/- 1 bursts/min) during the combination trial were not different from the algebraic sum of each trial performed alone (8 +/- 2 bursts/min). We conclude that the interaction for MSNA and arterial pressure is additive during combined vestibular and mental stimulation. Therefore, vestibular- and stress-mediated increases of MSNA appear to occur independently in humans.