Endogenous erythropoietin (EPO) secretion can still be modulated in patients with end-stage renal failure but only in response to strong stimuli. Thus even anephric dialysis patients are able to increase EPO production acutely when exposed to a marked hypoxic stimulus. The present study was designed to test the hypothesis that a decrease of plasma calcium or the administration of various antihypertensive agents might be able to induce acute changes of plasma EPO concentration. Four groups of chronic hemodialysis patients were studied. Eight patients volunteered for the induction of an acute, transient hypocalcemia via a calcium-free dialysate during the initial 60 min of a regular dialysis session of 240 min. Plasma immunoreactive (i) EPO, total calcium, and intact parathyroid hormone (iPTH<sub>1-84</sub>), as well as blood ionized calcium and blood gases were measured before as well as 30, 60,120 and 240 min after the start of dialysis. In addition, plasma iEPO was measured 48 h after the session. Patients of group 2 (n = 6), group 3 (n = 6), and group 4 (n = 7) received the day after a hemodialysis session a single dose of either acetazolamide, furosemide, or enalapril, respectively, and their plasma iEPO was determined before and 3, 6 and/or 24 h after drug administration. In group 1, plasma total calcium decreased from 2.39 ± 0.07 m M(mean ± SEM) to 1.98 ± 0.02 and 1.83 ± 0.03 m M after 30 and 60 min of dialysis, respectively, and blood ionized calcium from 1.28 ± 0.04 to 1.02 ± 0.03 and 0.92 ± 0.04 m M, respectively. Circulating iPTH rose from a basal value of 96 ± 27 pg/ml to 431 ± 154 and 374 ± 156 pg/ml at 30 and 60 min, respectively. Plasma iEPO levels were however unchanged during the 60 min of calcium-free dialysis and thereafter (21.8 ± 1.2 vs. 21.8 ± 1.3 mU/ml at 0 and 60 min, respectively), as were blood gases and pH. After the administration of hypertensive agents, there was also no acute change of plasma iEPO except for furosemide (group 3) where a borderline decrease of plasma iEPO was observed after 6 h (from initially 51.6 ± 11.6 to 31.4 ± 4.3 mU/ml, p < 0.06). In conclusion, neither the induction of hypocalcemia nor the administration of antihypertensive agents lead to acute changes of plasma iEPO levels in chronic hemodialysis patients.