The present study aimed to assess the influence of acetate (AC) and bicarbonate (BI) hemodialysis with a cuprophane membrane on plasma erythropoietin (EPO) levels in 30 patients with chronic renal failure (CRF). Fifteen patients were severely anemic with an Hct below 30%, while 13 were moderately anemic with an Hct equal to or more than 30%. None had received rHuEPO or ACE inhibitors before the study. Blood samples for EPO and pO2 estimation were withdrawn before and after 1, 2 and 5 h of AC dialysis. In 11 of the patients with an Hct < 30% the same protocol was repeated during BI dialysis. In spite of a significant decrease in pO2 during the first hour of AC dialysis, the plasma EPO concentration decreased significantly in both severely and moderately anemic CRF patients from 35.4 +/- 2.6 to 23.6 +/- 3.5 mU/ml after 5 h of hemodialysis (p = 0.0001 by paired t-test) and from 39.5 +/- 8.6 to 27.5 +/- 8.9 mU/ml (p < 0.01) respectively. In contrast to AC dialysis, Bi dialysis failed to change the plasma EPO concentration (from 32.3 +/- 4.1 to 30.3 +/- 4.7 mU/ml after 5 h of hemodialysis). Conclusions AC but not BI hemodialysis shows a significant suppressive effect on plasma EPO levels in anemic CRF patients in spite of a significant decline in pO2. Factors other than pO2 seem to be involved in the regulation of EPO secretion in CRF patients during AC dialysis.