It has been suggested that the well known analgesic effect of calcitonin (CT) may result from an enhanced secretion of opioid peptides. The purpose of this double-blind, controlled study was therefore to evaluate the effectiveness of CT on the opiate withdrawal syndrome. 20 drug addicts were randomly allocated to receive either 200 UI/day of salmon CT (n = 10) or placebo (n = 10) by nasal spray, after the abrupt withdrawal of low-dose methadone (20 mg/day). The severity of the withdrawal syndrome was evaluated by means of a score derived from a symptom check-list. Plasma beta-endorphin, glucose and insulin levels were measured before and after CT administration. The subjects treated with spray CT had significantly lower score than those treated with placebo. Beta-endorphin levels did not show any significant variation in both groups. An inhibitory action of CT on insulin secretion was observed. Our data suggested that CT might be considered a useful supportive measure for opiate withdrawal. CT action does not seem to involve the opioid system, but is probably mediated by a direct action on specific receptors or by a modulation of noradrenergic pathways.