1. We studied the acute effects of intranasal and subcutaneous calcitonin in 40 patients with active Paget's disease of bone. Patients received a single dose of either 400 units of calcitonin delivered as a nasal spray, or 1, 10 or 100 units of subcutaneous calcitonin, or placebo. 2. Subcutaneous salmon calcitonin, administered at doses of 1, 10 and 100 units to nine patients with Paget's disease of bone, induced a dose-dependent fall in the serum calcium. This calcium-lowering effect was not seen with a second group of nine patients receiving placebo. 3. The lower doses of calcitonin had significant effects, and these were more pronounced in patients with lower rates of bone turnover. 4. Four hundred units of calcitonin administered as a nasal spray induced effects qualitatively similar to those seen with subcutaneous calcitonin, with an efficacy equivalent to approximately 30 units of subcutaneous calcitonin. 5. We conclude that the bioequivalence of calcitonin given by intranasal insufflation is low compared with its parenteral administration. The intranasal route may be more appropriate for managing patients with disorders associated with low bone turnover.