To clarify the reason for the therapeutic efficacy of Elcatonin (eCT), an eel calcitonin derivative, in rheumatoid arthritis (RA), we studied the effect of eCT on the extracellular (EC) release and intracellular (IC) production of interleukin-1 (IL-1) by peripheral blood monocytes from patients with RA. In vitro treatment of RA monocytes with eCT reduced predominantly the EC release of both IL-1 alpha and IL-1 beta. Moreover, EC release and IC production of IL-1 alpha and IL-1 beta by monocytes from RA patients who received non-steroidal anti-inflammatory drugs (NSAIDs) plus eCT (CT group) were significantly lower than in those who received NSAIDs only (NSAID group). The anti-rheumatic effect of eCT may be mediated via the inhibition of EC release and the IC production of IL-1 from RA patients.