Swimming at 25–30 °C for 30 min stimulates release of β-endorphin from both the anterior and intermediate lobe of the pituitary in rats. Measurement of N-acetyl β-endorphin-immunoreactivity (IR), which is specific for intermediate lobe secretion, indicates a 2- to 3-fold increase in N-acetyl β-endorphin IR in plasma following this challenge. When swim is repeated on a daily basis, there is an increase in the amount of N-acetyl β-endorphin IR released with repeated swim over time. As well as increased response to the swim challenge, these animals demonstrate an increase in the resting plasma levels of N-acetyl β-endorphin IR and an increase in the intermediate lobe content of N-acetyl β-endorphin IR. Molecular sieving of plasma from rats which were swum repeatedly demonstrates that this N-acetyl β-endorphin IR consists of both larger molecular weight N-acetyl β-endorphin IR, e.g. N-acetyl β-endorphinι_3i and C-terminally shortened forms, e.g. N-acetyl β-endorphin1–27- Administration of propranolol (3 mg/ kg), a β-adrenergic antagonist, 30 min before the onset of swim is able to block the intermediate lobe release of N-acetyl β-endorphin IR with acute swim challenge. However, repeated administration of propranolol in conjunction with repeated swim is not able to block the swim stress-induced increase in plasma N-acetyl β-endorphin IR or the increase in N-acetyl β-endorphin IR content of the intermediate lobe. This is not due to decreased sensitivity to propranolol with repeated administration since in rats given chronic propranolol treatment an acute dose of propranolol is still able to block swim stress-induced release of N-acetyl β-endorphin IR. Similarly, it is not due to a decreased efficacy of this dose of propranolol in rats which w