In volunteers the activity of various doses of a nasal spray and of a suppository of salmon calcitonin was compared to a placebo and to the parenteral route of administration. Both new modes of administration were found to be active on the kidney (and the suppository was found to affect bone turnover as well). The parenteral route proved more effective, but the nasal and/or rectal routes were devoid of systemic side effects and had minimal local intolerance. The nasal spray was used at 200 units daily in 15 patients with Paget's disease, and at 400 units daily in another nine patients, both trials lasting one year. The two regimens proved active on the parameters of bone turnover and the higher dose was more effective than the lower one. Similarly, a 300 unit suppository was given to another 12 patients. This trial is still being completed at this time. At the third month of therapy, the parameters of bone turnover were significantly depressed. Both new modes of therapy were able to improve the focal bone balance of the osteolytic lesions monitored on sequential roentgenograms. Systemic side effects were absent and local side effects were minimal. Only one patient interrupted the nasal spray therapy, and no one interrupted the suppository therapy.