Recently we showed that both acute metabolic and respiratory acidosis stimulate parathyroid hormone (PTH) secretion in the dog. To evaluate the specific effect of acidosis, ionized calcium (iCa) was clamped at a normal value. Because iCa values normally increase during acute acidosis, we now have studied the PTH response to acute metabolic and respiratory acidosis in dogs in which the iCa concentration was allowed to increase (non-clamped) as compared to dogs with a normal iCa concentration (clamped). Five groups of dogs were studied: control, metabolic (clamped and non-clamped), and respiratory (clamped and non-clamped) acidosis. Metabolic (HCl infusion) and respiratory (hypoventilation) acidosis were progressively induced during 60 minutes. In the two clamped groups, iCa was maintained at a normal value with an EDTA infusion. Both metabolic and respiratory acidosis increased (P<0.05) iCa values in non-clamped groups. In metabolic acidosis, the increase in iCa was progressive and greater (P<0.05) than in respiratory acidosis in which iCa increased by 0.04 mM and then remained constant despite further pH reductions. The increase in PTH values was greater (P<0.05) in clamped than in non-clamped groups (metabolic and respiratory acidosis). In the non-clamped metabolic acidosis group, PTH values first increased and then decreased from peak values when iCa increased by more than 0.1 mM. In the nonclamped respiratory acidosis group, PTH values exceeded (P<0.05) baseline values only after iCa values stopped increasing at a pH of 7.30. For the same increase in iCa in the non-clamped groups, PTH values increased more in metabolic acidosis. In conclusion, 1) both metabolic and respiratory acidosis stimulate PTH secretion; 2) the physiologic increase in the iCa concentration during the induction of metabolic and respiratory acidosis reduces the magnitude of the PTH increase; 3) in metabolic acidosis, the increase in the iCa concentration can be of sufficient magnitude to reverse the increase in PTH values; and 4) for the same degree of acidosis-induced hypercalcemia, the increase in PTH values is greater in metabolic than in respiratory acidosis.