Microvascular dysfunction precedes the clinical manifestations of cardiovascular disease. Given the ethnic disparities in cardiovascular disease, we aimed to investigate ethnic differences in microvascular endothelial function in a group of young (18-33years old), apparently healthy individuals (n=33, nine Black African, 12 mixed ancestry and 12 Caucasian). Microvascular endothelium-dependent and -independent function was assessed by laser Doppler imagery and iontophoresis of ACh and sodium nitroprusside (SNP), respectively, adjusting for skin resistance. Microvascular reactivity was expressed as maximum absolute perfusion, percentage change from baseline and area under the curve (AUC). Skin resistance was significantly lower in the Caucasian group in response to ACh (Caucasian, mean 0.16±0.03Ω versus Black, 0.21±0.04Ω and mixed ancestry, 0.20±0.02Ω, P<0.01) and SNP (Caucasian, 0.08±0.01Ω versus Black, 0.11±0.02Ω and mixed ancestry, 0.12±0.01Ω, P<0.01). Microvascular function in response to ACh was significantly higher in the Caucasian group compared with the other two groups; however, after adjusting for skin resistance these differences were no longer significant. Conversely, the microvascular SNP response remained significantly higher in the Caucasian group, even after adjusting for skin resistance (P<0.01). Diastolic blood pressure was inversely associated with the AUC of ACh (r=-0.4) and all SNP responses (r=-0.3 to -0.6). Skin resistance was inversely associated with AUC and maximum absolute ACh response (r=-0.59 and -0.64, respectively) and all SNP responses (r=-0.37 to -0.79). Ethnic differences in endothelium-independent microvascular function may contribute to ethnic disparities in cardiovascular disease. Moreover, skin resistance plays a significant role in the interpretation of the microvascular response to outcomes of iontophoresis in a multiethnic group.