Ether stress or intracerebroventricular (i.c.v.) administration of saline, met-enkephalin, or naltrexone raised plasma corticosterone levels in mice. The response to ether stress was abolished by a preceding ether stress or by pretreatment with i.c.v. saline or naltrexone. However, following i.c.v. met-enkephalin, plasma corticosterone was significantly elevated by ether stress, the effect being blocked by simultaneous injection of met-enkephalin and naltrexone. Met-enkephalin appears to prevent fast-feedback inhibition of the hypothalamus-pituitary-adrenal system.