Twenty minutes of submaximal treadmill running was associated with an elevation in plasma levels of beta-endorphin immunoreactivity (P less than 0.02). This increase was greater in men (14.9 +/- 3.4 fmole/ml) than women (2.6 +/- 1.2 fmole/ml)(P less than 0.05). Plasma levels of ACTH and growth hormone also increased after running. ACTH increased more in men (7.8 +/- 1.1 fmole/ml) than in women (1.1 +/-0.44 fmole/ml)(P less than 0.02). There was a similar growth hormone response in both sexes. No correlation can at this time be made with levels in the central nervous system. Changes in plasma levels of beta-endorphin immunoreactivity may be responsible for some of the euphoria and analgesia anecdotally associated with running.