Biological activity of eel calcitonin 100 IU administered by the rectal route was evaluated in healthy volunteers by measuring plasmatic variations of cyclic adenosine monophosphate (cAMP) after a single dose and during a 21-day treatment. This formulation appears to allow a bioavailability of the drug which is half of the same dose administered intramuscularly, and to cause a prompt and significant increase of plasma cAMP, with minimal variations of calcaemia. Repeated administration shows the persistence in time of this effect. The overall conclusion is that the amount of calcitonin absorbed through the rectal mucosa seems sufficient to induce a typical biological response related to the interaction of the hormone with its specific receptors in bone.