The aim of this study was to elucidate the diabetic hypocalcemia and PTH responsiveness, investigated by measuring blood ionized calcium and serum intact parathyroid hormone (S-PTH(1-84)) concentrations, before and during an induced and maintained controlled hypocalcemia. In 15 patients with insulin-dependent diabetes mellitus and 19 healthy volunteers the blood ionized calcium concentration was lowered by about 0.20 mmol/l and maintained at this level by blood ionized calcium controlled tri-sodium-citrate infusion. In patients vs controls, baseline measurements averaged for blood ionized calcium (mmol/l) 1.18 +/- 0.08 vs 1.24 +/- 0.03 (p < 0.01), for S-magnesium (mmol/l) 0.73 +/- 0.07 vs 0.81 +/- 0.07 (p < 0.01) and for S-PTH (1-84) (pmol/l) 3.0 +/- 1.0 vs 3.1 +/- 1.0 (p < 0.75). During the clamp, S-PTH (1-84) peaked to comparable maximums after 5-10 min in both groups and then declined to constant concentrations two to three times above their control levels. In conclusion, we found a diabetic hypocalcemia and hypomagnesemia, though baseline levels of PTH and PTH responsiveness were normal. This may be taken to indicate a mild shift downwards in the set-point for PTH secretion in patients with insulin-dependent diabeties mellitus.