Different types of calcitonin (porcine, human, salmon) are used in the management of bone diseases characterized by a high bone turnover, such as post-menopausal osteoporosis and Paget's disease; recently, salmon calcitonin has become clinically available as an intranasal (i.n.) spray. An analgesic effect has also been described for calcitonins, both in experimental animals and humans, but only a few studies in humans were placebo controlled. The aim of this study was to compare the analgesic efficacy of i.n. and intramuscular (i.m.) salmon calcitonin (sCT) and of placebo in women affected by painful post-menopausal osteoporosis, in a double-blind, double-placebo trial. Twenty-eight women were randomly allocated to one of the following treatments: 1) i.n. sCT 200 U/day plus i.m. placebo; 2) i.n. placebo plus i.m. sCT 100 U/day; and 3) i.n. and i.m. placebo. Each treatment lasted four weeks, and the pain score was evaluated weekly by means of a visual analogic scale (VAS). Twenty-four women completed the trial; with i.n. sCT, the pain score decreased significantly by the second week of treatment (p < 0.05); with i.m. sCT and with placebo, the pain score decreased significantly only by the fourth week (p < 0.05), so that the final pain scores obtained with the three treatments were not different. We conclude that i.n. sCT was probably more rapid, but not more effective than i.m. sCT or placebo in decreasing pain in post-menopausal osteoporosis.