It has been suggested that PTH-related peptide-(1-34) (PTHrP) is a regulator or modulator of regional or systemic cardiovascular function with varying vasodilating actions in different species. We have studied the cardiovascular pharmacodynamic profile of PTHrP in healthy humans. In a double blind, placebo-controlled, cross-over study design, eight healthy subjects were assigned to stepwise increased i.v. doses of PTHrP. In addition, a dose-response curve to PTHrP was constructed in a dorsal hand vein in eight subjects. PTHrP dose-dependently increased pulse rate and renal plasma flow by more than 50% (P < 0.0001 for both parameters, by ANOVA), but only a small venodilating response was seen in hand vein experiments, and no effect was noted on mean arterial blood pressure or cardiac inotropic performance. Although it is unlikely that PTHrP regulates systemic hemodynamics, its chronotropic effect and its potent action on renal plasma flow may represent the primary cardiovascular physiological targets of action.