To identify the factors influencing the serum concentrations and the peritoneal clearances of low molecular weight proteins (LMWP), fourteen patients on continuous ambulatory peritoneal dialysis (CAPD) for 1 to 57 (mean 9.4) months were examined. LMWP [Beta 2-microglobulin (Beta 2m, molecular wt 11.8 kD), cystatin C (cyst C, molecular wt 13.2 kD), Clara cell protein (CC16, molecular wt 15.8 kD), retinol-binding protein (RBP, molecular wt 21 kD) and alpha 1-microglobulin (Alpha 1m, molecular wt 33 kD)] and high molecular weight proteins (HMWP) [albumin (Alb, molecular wt 66 kD), immunoglobulins (IgG, molecular wt 170 kD and IgM, molecular wt 600 kD) and alpha 2-macroglobulin (Alpha 2m, molecular wt 718 kD)] were determined by latex immunoassay in the serum and dialysate collected during the peritoneal equilibration test (PET) with 2.27% dextrose (N = 14), and in dialysate from 56 standard exchanges, performed the day preceding PET, with 1.36% (N = 21), 2.27% (N = 23) and 3.86% (N = 12) dextrose. Determinants of serum concentrations and transperitoneal clearances of the proteins were traced by stepwise regression analysis using as possible contributors age, sex, residual diuresis, duration of the therapy (for serum concentrations), molecular radius of the protein and peritoneal membrane characteristics (for peritoneal clearances). LMWP serum concentrations were markedly increased whereas serum concentrations of HMWP were within the normal range. Residual diuresis, age and duration of dialysis emerged as significant determinants of serum concentration of some proteins, whereas transperitoneal clearance was dependent mainly on the size of the protein and, only for HMWP, on the dwell time. Residual diuresis was inversely related to the serum concentrations of four LMWP. Age was negatively correlated to the serum concentrations of beta 2m, CC16 and RBP. RBP and Alb were the only proteins whose serum concentration significantly decreased with time on CAPD. The relationship between peritoneal clearance and M(r) shows two slopes suggesting the existence of two populations of pores in the peritoneal capillary wall: small pores of about 20 to 25 A radius and large pores exceeding 100 A radius. A long dialysis cycle is associated with significant loss of HMWP only. Daily peritoneal protein losses, in mg (mean +/- SD), were as follows: Beta 2m 43.4 +/- 4.5; cyst C 9.6 +/- 1.8; CC16 1.8 +/- 0.3; RBP 58.9 +/- 11.1; Alpha 1m 149.5 +/- 15.7; Alb 6570 +/- 530; IgG 750 +/- 111; IgM 46.4 +/- 14.9; and alpha 2m 67.0 +/- 12.7. In conclusion, LMWP concentrations in the serum of patients on CAPD were markedly increased and influenced mainly by patient-related factors (residual diuresis and age). Serum albumin and RBP declined with the duration of dialysis. Peritoneal protein loss was determined by the size of the protein and, for large proteins, by the dwell time. The peritoneum behaves as a membrane with at least two populations of pores.