1. Administration of highly purified bovine parathyroid hormone (BPTH) (200 MRC units) increased the concentration of adenosine 3′,5′-cyclic monophosphate (cyclic AMP) in the peripheral plasma of normal subjects within minutes, whether the hormone was given as a bolus injection or an infusion.
2. The subsequent disappearance of cyclic AMP from the circulation was also rapid (t1/2 = 14 min) and was associated with a prompt decline (t1/2 = 4.6 min) in the concentration of the ammo-terminal part of BPTH, as measured in a region-specific immunoradiometric assay.
3. The concentration of cyclic AMP in plasma from a renal vein was found to increase more rapidly and to reach a greater peak than plasma from a peripheral vein.
4. The administration of BPTH to anephric subjects caused no increase in cyclic AMP.
5. These investigations indicate that parathyroid hormone can act extremely rapidly, with a short half-life, and that the kidney makes a major contribution to the changes in plasma cyclic AMP induced by the hormone. In addition, they form the basis for the development of a simplified Ellsworth—Howard test, using changes in circulating cyclic AMP after BPTH administration as an index of responsiveness to the hormone.