Previous investigations of autoregulatory mechanisms in the control of skin blood flow suffer from the possibility of interfering effects of the autonomic nervous system. To address this question, in 11 subjects cutaneous vascular responses were measured during acute changes in perfusion pressure (using Valsalva maneuver; VM) before and after ganglionic blockade via systemic trimethaphan infusion. Cutaneous vascular conductance at baseline (CVC_base) and during the last 5 seconds of the VM (CVC_VM) were measured from forearm (non-glabrous) and palm (glabrous) skin. During the VM without ganglionic blockade, when compared to CVC_base, CVC_VM decreased significantly at the palm (0.79±0.17 to 0.55±0.17 AU/mmHg, P=0.002) but was unchanged at the forearm (0.13±0.02 to 0.16±0.02 AU/mmHg, P=0.50). After ganglionic blockade, VM induced pronounced decreases in perfusion pressure, which resulted in significant increases in CVC_VM at both forearm (0.19±0.03 to 0.31±0.07 AU/mmHg, P=0.008) and palm (1.84±0.29 to 2.76±0.63 AU/mmHg, P=0.003) sites. These results suggest that devoid of autonomic control both glabrous and non-glabrous skin are capable of exhibiting vasomotor autoregulation during pronounced reductions in perfusion pressure.