Objectives: The purposes of this study were to examine possible ethnic and sex differences in plasma ET-1 levels at rest and in response to acute stress and to examine relationships between ET-1 and vasoconstrictive-mediated BP reactivity to stress. Methods: Two hundred twenty-two adolescents (mean age = 18.5 ± 2.8 years; 130 [70 males] EAs and 92 [48 males] AAs) completed two stressors (video game, forehead cold). Hemodynamic measures and blood samples were collected at catheter insertion and before and immediately after the two stressors, separated by 20-minute rest periods. Results: AAs and males exhibited higher levels of SBP and DBP and of TPRI and ET-1 at each sampling point compared with EAs and females, respectively (p values < .001). AAs and males exhibited greater increases in SBP, TPRI, and ET-1 in response to each stressor (p values < .05). Intraindividual correlations between ET-1 and hemodynamic parameters revealed that most individuals exhibited a positive association between ET-1, BP, and TPRI. However, some individuals exhibited a negative association between ET-1 and the above-mentioned hemodynamics, suggesting a compensatory vasodilation mechanism. Conclusion: The findings demonstrate significant sex and ethnicity differences in stress-induced vasoconstrictive peptide release and support the hypothesis that these differences may be important in explaining the ethnicity and sex differences in the prevalence of cardiovascular disease.