Salmon calcitonin (s-CT) has been shown to be a valuable analgesic in phantom limb pain (PLP) in several case reports. To evaluate these findings a double-blind crossover comparison of s-CT treatment versus placebo was initiated. Twenty-one out of 161 patients who had undergone major amputations and developed severe PLP 0-7 days after surgery were included in the study. For each patient a matched pair of infusions was prepared containing either 200 IU of s-CT or placebo. Group I (n = 11) was first given s-CT and group II (n = 10) placebo. When PLP reached a level of more than 3 on a numeric analogue scale (NAS) the first infusion was administered. The second infusion (crossover) or more infusions were given when the pain level again exceeded more than 3 on NAS. Using s-CT infusion, PLP was eased from a median of 7 to 4 on NAS in both groups (P less than 0.001), regardless of whether s-CT or placebo was given first. Placebo, however, did not change pain scores (median 7 on NAS, P greater than 0.1). In the s-CT group, but not in the placebo group, 4 individuals remained pain free without a second infusion. Any further treatment was performed with s-CT. One week after the first PLP treatment 19 patients (90%) had pain relief of more than 50%, 16 (76%) were completely pain free, and 15 (71%) never experienced PLP again. One year later 8 out of the 13 surviving patients (62%) still had more than 75% PLP relief. After 2 years PLP exceeded 3 on NAS in 5 individuals (42%), and the remaining 12 patients presented the same PLP as after 1 year. In conclusion, s-CT is a valuable treatment for PLP in the early postoperative period.