It has been suggested that the analgesic action of calcitonin (CT) might involve a stimulation of beta-endorphin (beta-EP) release. To verify whether salmon CT modifies the circulating levels of beta-EP, and whether the route of administration plays any role in this response, we have studied 10 healthy male volunteers, aged 30-40 yr. Each of them was studied on 4 different days, after administration of placebo or salmon CT (100 UI) by the intravenous, intramuscular and nasal route, in random order. Ionized calcium tended to decrease, especially after intravenous CT, but there was no change in plasma beta-EP levels, regardless of the route of administration. It is therefore unlikely that circulating beta-EP mediates any biological effect of CT.