Context: Patients with classic congenital adrenal hyperplasia (CAH) have adrenomedullary dysplasia and hypofunction, and their lack of adrenomedullary reserve has been associated with a defective glucose response to brief high-intensity exercise. Objective: Our objective was to assess hormonal, metabolic, and cardiovascular response to prolonged moderate-intensity exercise comparable to brisk walking in adolescents with classic CAH. Subjects and Methods: We compared six adolescents with classic CAH (16-20 yr old) with seven age-, sex-, and body mass index group-matched controls (16-23 yr old) using a 90-min standardized ergometer test. Metabolic, hormonal, and cardiovascular parameters were studied during exercise and recovery. Results: Glucose did not change throughout exercise and recovery for controls, whereas CAH patients showed a steady decline in glucose during exercise with an increase in glucose in the postexercise period. Glucose levels were significantly lower in CAH patients at 60 (P = 0.04), 75 (P = 0.01), and 90 (P = 0.03) min of exercise and 15 (P = 0.02) min post exercise, whereas glucose levels were comparable between the two groups early in exercise and at 30 min (P = 0.19) post exercise. As compared with controls, CAH patients had significantly lower epinephrine (P = 0.002) and cortisol (P ≤ 0.001) levels throughout the study and similar norepinephrine, glucagon, and GH levels. Patients with CAH and controls had comparable cardiovascular parameters and perceived level of exertion. Despite having lower glucose levels, insulin levels were slightly higher in CAH patients during the testing period (P = 0.17), suggesting insulin insensitivity. Conclusion: CAH patients have defective glycemic control and altered metabolic and hormonal responses during prolonged moderate-intensity exercise comparable to brisk walking.