Many earlier human studies have reported that increasing the tilt angle of head-up tilt (HUT) results in greater muscle sympathetic nerve activity (MSNA) response, indicating the amplitude-dependence of sympathetic activation in response to orthostatic stress. However, little is known about whether and how the inclining speed of HUT influences the MSNA response to HUT, independent of the magnitude of HUT. Twelve healthy subjects participated in passive 30 HUT tests at inclining speeds of 1 (CONTROL), 0.1 (SLOW) and 0.0167 (VERYSLOW) -°/sec. We recorded muscle SNA (MSNA, tibial nerve) by microneurography, and assessed non-stationary time-dependent changes of R-R interval variability using complex demodulation technique. MSNA averaged over every 10-degree tilt angle increased during inclination from 0° to 30°, with smaller increases in the SLOW and VERYSLOW tests than in the CONTROL test. Although a 3-min MSNA overshoot after reaching 30° HUT was observed in the CONTROL test, no overshoot was detected in the SLOW and VERYSLOW tests. In contrast with MSNA, increases in heart rate during the inclination and after reaching 30° were similar in these tests, probably because as compred with CONTROL test, greater increases in plasma epinephrine counteracted smaller autonomic responses in the VERYSLOW test. These results indicate that slower HUT results in lower activation of MSNA, suggesting that HUT-induced sympathetic activation depends partially on the speed of inclination during HUT in humans.