Hypohydration decreases cutaneous vasodilation and sweating during heat stress, but it is unknown if these decrements are from postsynaptic (i.e. sweat gland/blood vessel) alterations. Purpose: To determine if hypohydration affects postsynaptic cutaneous vasodilation and sweating responses. Methods: 12 healthy men participated in euhydrated (EU) and hypohydrated (HY) trials, with hypohydration induced via fluid restriction and passive heat-stress. Changes in cutaneous vascular conductance (CVC; %max) in response to incremental intradermal infusion of the endothelium-independent vasodilator sodium nitroprusside (SNP) and the endothelium-dependent vasodilator methacholine chloride (MCh) were assessed by laser Doppler flowmetry. Local sweat rate (LSR) was simultaneously assessed at the MCh site via ventilated capsule. At the end of the last dose, maximal CVC was elicited by delivering a maximal dose of SNP (5x10-2 M) for 30 min to both sites with simultaneous local heating (~44°C) at the SNP site. The concentration of drug needed to elicit 50% of the maximal response (Log EC50) was compared between hydration conditions. Results: %BM loss was greater when HY vs. EU (-2.2 ± 0.7 vs. -0.1 ± 0.7%, P < 0.001). Log EC50 of endothelium-dependent CVC was lower when EU (-3.62 ± 0.22) versus HY (-2.93 ± 0.08; P = 0.044). Hypohydration did not significantly alter endothelium-independent CVC or LSR (both P > 0.05). Conclusion: Hypohydration attenuated endothelium-dependent CVC but did not affect endothelium-independent CVC or LSR responses. These data suggest that reductions in skin blood flow accompanying hypohydration can be partially attributed to altered postsynaptic function.