OBJECTIVE To evaluate the hypothalamo-pituitary-adrenal (HPA) response to both mild and intense exercise. METHODS Maximum oxygen consumption (VO2max.) was initially determined. Exercise to 20% (mild) and 90% (intense) VO2max. was undertaken in random order. Subjects were exercised over a 5-minute period to the required level of intensity, which was maintained for a further 10 minutes. METHODS Six trained male athletes. METHODS Brachial vein blood was sampled before and at 5-minute intervals during and after exercise and assayed for plasma cortisol, ACTH, arginine vasopressin (AVP), corticotrophin releasing factor (CRF), sodium and lactate levels. Haemoglobin and haematocrit were measured before and at the end of exercise. Heart rate was monitored continuously and blood pressure measured whenever blood was sampled before and after exercise. RESULTS Maximum heart rate was 184 +/- 2 and 82 +/- 5 (mean +/- SEM) beats per minute at 90 and 20% VO2max. respectively. Plasma volume fell by 8.7 +/- 2.4% with intense exercise. Significant increases in plasma concentrations of AVP, ACTH and cortisol, but not CRF, occurred during intense exercise. Plasma sodium concentration, which increased during intense but not mild exercise, peaked at 10 minutes after the onset of exercise and preceded the rise in plasma AVP. The AVP peak clearly preceded the ACTH peak in two subjects and occurred synchronously with it in three subjects. CONCLUSIONS These results indicate that although significant HPA activation occurs during intense exercise, CRF does not appear to play a major role in mediating the ACTH response to an acute episode of vigorous exercise in man. AVP may be more important in this regard.