Background and Purpose: Nitric oxide (NO)/endothelin imbalance may play a role in the regulation of cerebral blood flow. The aim of the present study was to assess whether these endothelial factors influence middle cerebral artery blood flow velocities (MCAV) and cerebrovascular reactivity (CVR) in healthy and hypertensive adolescents. Subjects and Methods: 106 adolescents (61 hypertensive and 45 normotensive) underwent transcranial Doppler measurements of the middle cerebral artery at rest and after 30 s of breath-holding (BH) and 60 s of hyperventilation (HV). Additionally, NO and endothelin-1 (ET-1) concentrations of the serum were assessed. The correlation between NO and ET-1 levels as well as MCAV and CVR values was analyzed. Results: Resting MCAVs were higher among hypertensive teenagers (76.5 ± 24 vs. 62.8 ± 15.6 cm/s, respectively, p < 0.001). CVR values did not differ between hypertensive and healthy adolescents after the BH and HV procedure. A significant negative correlation was found between absolute MCAV values and NO concentrations. ET-1 was positively related to MCAV. Conclusions: Cerebral blood flow velocities, but not CVR values, are associated with serum NO and ET-1 concentrations in adolescents.