Prior exposure to excess PTH desensitizes the kidney to subsequent doses of the hormone. We tested the hypothesis that prior deficiency of PTH would increase renal responsiveness to the agent. Ten normal subjects and nine patients with treated chronic postsurgical hypoparathyroidism received infusions of synthetic human PTH fragment 1-34 [hPTH-(1-34), Armour], 200 U over 10 min. All subjects responded to hPTH-(1-34) infusion with marked increases in plasma and urinary cAMP and phosphaturia. Mean (and median) urinary cAMP responses in the hypoparathyroid subjects were 62% (and 91%) above the responses in normal subjects, while mean (and median) nephrogenous cAMP responses were 65% (and 88%) higher than those in normal subjects. Mean (and median) phosphaturic responses to hPTH-(1-34) in hypoparathyroidism were 49% (and 52%) above normal subjects' responses. All of these differences were statistically significant. These data and others from the literature suggest that chronic hypoparathyroidism enhances renal responses to PTH, consistent with the concept of hormonal regulation of tissue sensitivity to the hormone.