Recent studies from several laboratories have suggested that the cardiovascular system may be considered a new target organ system for parathyroid hormone (PTH). PTH caused a sharp, dose-dependent reduction in blood pressure of several mammalian models. This hypotensive response was mediated by direct interaction of PTH with the vascular smooth muscle of arteries and resistance vascular beds. Increases in intracellular cyclic AMP concentrations were temporally and quantitatively correlated with smooth muscle relaxation by PTH. Direct (nonreflex) positive inotropic and chronotropic effects have been observed in cardiac tissue after treatment with PTH. Considering these and other observations, a physiological role for PTH as a homeostatic regulator of the cardiovascular system may be speculated.