This study was designed to assess effects of exercise on plasma and cerebrospinal fluid (CSF) levels of immunoreactive (ir) beta-endorphin, ACTH, cortisol, norepinephrine, and glucose in the conscious dog. Dogs were exercised on a treadmill at low or high intensity (4.2 miles/h and a 6% or 20% incline) for 90 min, and were allowed to recover for 90 additional min. Neither intensity of exercise changed plasma glucose levels, but dose-related changes in glucose kinetics did occur. CSF glucose declined in both groups. During low intensity exercise, plasma levels of ir-beta-endorphin, ACTH, and cortisol increased with duration of exercise. During high intensity exercise, ACTH, ir-beta-endorphin and cortisol increased faster, and the integrated plasma response of these hormones was greater. Thus, peripheral release of ir-beta-endorphin, ACTH, and cortisol during exercise is dose-related with respect to time and intensity. CSF ir-beta-endorphin and ACTH both increased during low- but not high-intensity exercise. CSF cortisol rose markedly in both exercise groups. During high-intensity exercise there was a 50% increase in CSF norepinephrine, indicating that exercise induces alterations in central noradrenergic turnover. We conclude that exercise is a physiologic regulator of both peripheral and central neuroendocrine systems.