Consumption of a high-fat (HF) meal has been shown to reduce flow-mediated dilation (FMD) in men, but not women. This decline in FMD may be a result of decreased nitric oxide (NO) bioavailability. NO inhibits sympathetic vasoconstriction and a HF meal may, therefore, heighten sympathetic vasoconstrictor responsiveness. However, the effect of a HF meal on sympathetic vasoconstriction in men and women has not been investigated. PURPOSE: The purpose of this study was to investigate the hypothesis that consumption of a HF meal would heighten sympathetic vasoconstrictor responsiveness in men, but have no effect in women. METHODS: In a randomized cross-over design, young males (n=15) and females (n=15) consumed a HF or an isocaloric low-fat (LF) meal on separate days. Two hours post-meal, subjects underwent a cold pressor test (CPT) and measurement of brachial artery FMD to determine sympathetic vasoconstrictor responsiveness and endothelial function, respectively. Beat-by-beat blood pressure was measured by Finometer and mean arterial pressure (MAP) was calculated. Forearm blood flow (FBF) was measured by Doppler ultrasound at the brachial artery and forearm vascular conductance (FVC) was calculated as FBF/MAP. Sympathetic vasoconstrictor responsiveness was calculated as the percentage decrease in FVC (%∆FVC) in response to CPT. FMD was calculated as the percentage increase in brachial artery diameter from baseline and normalized for cumulative shear rate. RESULTS: Sympathetic vasoconstrictor responsiveness was not different (p>0.05) between meal conditions or between females (LF: -27±14%: HF: -30±15%) and males (LF: -29±23%: HF: -24±16%) in either meal condition. FMD was higher (main effect of sex; p<0.05) in females (LF: 8.1±2.1%: HF: 7.4±1.4%) compared to males (LF: 6.2±1.5%: HF: 5.1±1.1%) and FMD was lower (main effect of meal; p<0.05) in the HF compared to the LF meal condition. No interaction (p>0.05) was observed between meal condition and sex for FMD. FMD normalized for shear rate was not different (p>0.05) between meal conditions or between females and males in either meal condition. CONCLUSION: These data suggest that, despite evidence of a post-prandial decrease in endothelial function, a HF meal does not alter sympathetic vasoconstrictor responsiveness in men or women.