The objective of this study was to examine if the Cica clamp technique, sequential citrate and calcium administration sufficient to promote steady-state-blood-ionized calcium concentrations (B-Ca2+) of about 0.20 mmol/l below and above the individual baseline concentrations, was able to produce reciprocal changes in serum intact parathyroid hormone [S-PTH(1-84)] in chronic surgical hypoparathyroidism (HP; n = 10) and chronic idiopathic HP (n = 2). The calcium set point according to Brown [J Clin Endocrinol Metab 1993;56:572-581] was calculated when possible. Data from 22 controls were included for comparison. Within 5-10 min B-Ca2+ lowering in responding patients with surgical HP (n = 7) and controls demonstrated transient S-PTH(1-84) peaks from 1.3 +/- 0.7 to 3.5 +/- 3.2 pmol/l (p < 0.05) and from 3.4 +/- 1.2 to 19.1 +/- 6.7 pmol/l (p < 0.001), respectively. Subsequently S-PTH(1-84) declined to steady-state hypersecretion levels of about 1.9 +/- 1.2 and 8.6 +/- 2.6 pmol/l, respectively. An increase of B-Ca2+ made S-PTH(1-84) unmeasurable in all HP responders except one, while S-PTH(1-84) remained measurable, 0.9 +/- 0.4 pmol/l, in all controls. In responding patients with surgical HP and controls the respective calcium set points averaged 1.05 +/- 0.06 and 1.13 +/- 0.04 mmol/l, respectively (p < 0.001). The remaining nonresponders with surgical and idiopathic HP did not respond at all. To summarize, 7 out of 10 patients with surgical HP demonstrated a normal pattern of parathyroid response to sequential B-Ca2+ decreases and increases.(ABSTRACT TRUNCATED AT 250 WORDS)