Renal responsiveness to synthetic human parathyroid hormone (HPTH) 1-38 was examined in seven healthy volunteers. Each subject received three different doses (35 micrograms, 17.5 micrograms, 8.75 micrograms) as bolus intravenous injections. Rapid, transient, dose-dependent decreases in diastolic blood pressure and increases in heart rate were observed, as reported previously in animal studies, suggesting an acute vasodilatory effect of the hormone. The extracellular cyclic AMP responses were brisk and dose-dependent in the group as a whole as well as in the individual subjects. In contrast, the phosphaturic responses, though statistically significant with all three doses, were of a lesser magnitude and showed an individual variability. Nearly maximal decreases in TmP/GFR were found even after the lowest dose with minimal increases in cyclic AMP in some subjects. The injections of HPTH 1-38 also induced a dose-dependent natriuresis which was accompanied by an increase in excreted calcium. It seems that under these experimental conditions the sodium-dependent renal calcium transport cannot be compensated by the effects of the hormone on the distal tubule. HPTH 1-38 can be safely and predictably used for the assessment of renal responsiveness to PTH in routine clinical practice.