Plasma immunoreactive atrial natriuretic factor (ANF) levels, their chromatographic profiles (high-performance liquid chromatography; HPLC) and changes during sequential ultrafiltration (UF; 1 litre/h) and biochemical correction without fluid removal (BC; 3 h) were studied in 8 end-stage chronic renal failure patients on intermittent haemodialysis ( > 1 year). Patients entered randomly the UF-BC or BC-UF protocols that were reversed after 1 week. HPLC showed a single peak of ANF immunoreactivity in plasma of end-stage chronic renal failure patients before dialysis sessions. ANF at the end of fluid removal fell by 31 ± 2% (p < 0.01) during UF-BC and by 30 ± 2% (p < 0.01) at the end of BC during BC-UF. In both sequences a further slight reduction in plasma ANF was observed during the second phase: it was 8.5 ± 5% (n.s.) during BC of the BC-UF and 12.5 ± 2% (p < 0.05) during fluid removal of BC-UF. Plasma ANF was not significantly removed by the machinery. BC did not modify the microhaematocrit in the BC-UF sequence while the microhaematocrit was significantly increased by UF (13 ± 1 and 14 ± 1%, p < 0.005 vs. basal, respectively), and decreased by BC in the UF-BC sequence (-5 ± 2% vs. end UF, p < 0.05). Serum creatinine and urea decreased significantly during BC in both protocols while they were unmodified during UF. No significant changes were seen in PRC during either protocol. Our results indicate that circulating levels of ANF in end-stage chronic renal failure patients, may be regulated by humoral factors in addition to the already well-known mechanisms such as plasma volume and right atrial pressure.