We sought to determine whether oxidative stress or a relative deficit of l-arginine plays a role in reducing cutaneous vasodilation in response to local heating in chronic kidney disease (CKD). Eight patients with stage 3-4 CKD and eight age- and sex-matched healthy control (HC) subjects were instrumented with four microdialysis (MD) fibers for the local delivery of 1) Ringers solution (R), 2) 20 mM ascorbic acid (AA), 3) 10 mM l-arginine (l-Arg), and 4) 10 mM N(G)-nitro-l-arginine methyl ester (l-NAME). Red blood cell (RBC) flux was measured via laser Doppler flowmetry. A standardized nonpainful local heating protocol (42°C) was used. Cutaneous vascular conductance (CVC) was calculated as RBC flux/MAP and all data were expressed as a percentage of the maximum CVC at each site (28 mM sodium nitroprusside, T(loc) = 43°C). The plateau %CVC(max) was attenuated in CKD (CKD: 76 ± 4 vs. HC: 91 ± 2%CVC(max); P < 0.05) and the NO contribution to the plateau was lower in CKD (CKD: 39 ± 7, HC: 54 ± 5; P < 0.05). The plateau %CVC(max) in the CKD group was significantly greater at the AA and l-Arg sites compared with R (AA: 89 ± 2; l-Arg: 90 ± 1; R: 76 ± 4; P < 0.05) and did not differ from HC. Initial peak %CVC(max) was also significantly attenuated at the R and l-Arg sites in CKD (P < 0.05) but did not differ at the AA site. These results suggest that cutaneous microvascular function is impaired in stage 3-4 CKD and that oxidative stress and a deficit of l-arginine play a role in this impairment.