This study compared the rates of whole-body proteolysis and of albumin and fibrinogen synthesis of seven hemodialysis patients (HD) with those of seven normal matched control subjects (C). HD patients had a normal nutritional and inflammatory status and serum albumin levels >3.5 g/dl. Endogenous leucine flux, albumin and fibrinogen fractional synthesis rate (FSR), and absolute intravascular synthesis rate (ASR) of albumin and fibrinogen all were evaluated by a primed/continuous infusion of 5,5,5-D3-L-leucine. Plasma volume was determined by the Evans blue dye dilution method. Endogenous leucine flux was significantly increased in HD (2.64 +/- 0.08 micromol/kg per min) compared with C (2.17 +/- 0.07 micromol/kg per min, P: < 0.05). Serum albumin concentrations were similar in HD and C. Plasma fibrinogen levels were significantly increased in HD compared with C (P: < 0.05). Plasma volume was greater in HD than in C (P: < 0.05). As a result, total intravascular pool of both albumin (141 +/- 7 versus 114 +/- 3 g/1.73 m(2), P: < 0.05) and fibrinogen (11.7 +/- 1 versus 6.7 +/- 0.5 g/1.73 m(2), P: < 0.05) were greater in HD than in C. Albumin FSR was not statistically different in HD and C. However, albumin ASR was significantly increased in HD than in C (13.7 +/- 2 versus 10.3 +/- 1 g/1.73 m(2) per d, P: < 0.05). Similarly, FSR of fibrinogen did not differ in HD and C groups, whereas ASR of fibrinogen was significantly higher in HD than in C (3.31 +/- 0.6 versus 1.94 +/- 0.3 g/1.73 m(2) per d, P: < 0.05). In summary, normoalbuminemic HD patients have an increased intravascular pool with a greater absolute synthesis rate of both albumin and fibrinogen and an increased rate of whole-body leucine flux.