Background: Hypoalbuminemia is common in peritoneal dialysis (PD) patients; but the reduction in serum albumin levels (SAlb) that should be expected in stable PD patients is less clear. Objectives: To determine prospectively, in a group of stable Po patients without comorbid conditions, the changes in SAlb concentration and in the concentrations of the other serum protein fractions. To investigate the best determinants of a significant decrease in SAlb levels. Design: Prospective observational study. Methods: Seventeen PD patients in stable clinical condition, with no signs of systemic inflammatory response, were included in the study. SAlb and the electrophoretic pattern of serum proteins were determined immediately before PD start, and after 6, 9, 12, 15, 18, 21, and 24 months on Po. In each study period, clinical characteristics, adequacy parameters, protein catabolic rate (PNPNA: protein equivalent of non protein nitrogen appearance), and protein losses were determined. Patients were divided into two subgroups according to whether SAlb decreased less than 10%, or 10% or more, from baseline values after 24 months on Po, The main differences between the subgroups were investigated. Results: Mean SAlb did not decrease significantly after 24 months on Po (from baseline 3.99 +/- 0.46 g/dL to 3.80 +/- 0.54 g/dL), though percentage SAlb values did (58.36% +/- 5.58% vs 55.15% +/- 5.42%, p < 0.01). A weak increase in <alpha>(2)-globulin was observed after 18 months on Po (from 10.62% +/- 2.53% to 12.96% +/- 2.51%, p = 0.001). alpha (1)-Globulin showed a sustained increase from a mean baseline value of 3.51% +/- 1.09% to 6.83% +/- 2.13% after 24 months (p < 0.0001). Seven patients had a reduction in SAlb greater than 10% after 24 months on PD. Kt/V urea and residual renal function tended to be lower in patients whose SAlb decreased. Mean PNPNA was significantly lower in patients who had a reduction in SAlb (0.76 +/- 0.12 g/kg/day vs 0.96 +/- 0.12 g/kg/day, p < 0.0001). However, total protein loss was even greater in patients who had no SAlb reduction. Conclusions: After 24 months on PD, a mean reduction in SAlb of 10% -15% from baseline values should be expected only in those stable patients whose PNPNA is low.