The effects of acute treatment (i.p.) with selenium (Se) on glucoregulation, by measuring plasma levels of adrenocorticotropic hormone (ACTH), beta-endorphin (beta-EN), corticosterone (CORT) and glucose over time, were investigated. The hormones of the hypothalamic-pituitary adrenal (HPA) axis, were measured after treating rats with saline, Se: 1.6 mg/kg, or 3.8 mg/kg. Blood samples were collected before, 30, 60 and 90 min following injection. The results show that i.p. administration of Se (both doses) induce a rise in plasma ACTH, and beta-EN (P < 0.01). Plasma CORT and glucose levels also rose sharply by 30 min (P < 0.05). Corticosterone levels were increased in a dose-dependent fashion over the ensuing hour. Bilateral adrenal demedullation resulted in the abolishment of the Se-induced rise in plasma glucose. Pretreatment with metyrapone (300 mg/kg) was found to delay the Se-induced rise in plasma glucose. The results indicate that after a Se challenge the HPA axis is activated. In addition, CORT was found to be essential in the Se-induced rise in plasma glucose.