The transport of macromolecules during peritoneal dialysis is highly selective when they move from blood to dialysate but nearly completely unselective in the opposite direction. Aiming at describing this asymmetry, we modeled the peritoneal barrier as a series arrangement of two heteroporous membranes. First a three-pore membrane was considered, crossed by small [radius of the small pore (r(s)) approximately 45 A], large [radius of the large pore (r(L)) approximately 250 A], and transcellular pores accounting for 90, 8, and 2% to the hydraulic conductance, respectively, and with a corresponding pore area over diffusion distance (A(0)/Delta x) set to 50,000 cm. We calculated the second membrane parameters by fitting simultaneously the bidirectional clearance of molecules ranging from sucrose [molecular weight = 360, permeating solute radius (a(e)) approximately 5 A] to alpha(2)-macroglobulin (molecular weight = 820,000, a(e) approximately 90 A). The results describe a second two-pore membrane with very large pores (r(L) approximately 2,300 A) accounting for 95% of the hydraulic conductance, minor populations of small (r(s) approximately 67 A) and transcellular pores (3 and 2%, respectively), and an A(0)/Delta x approximately 65,000 cm. The estimated peritoneal lymph flow is approximately 0.3 ml/min. The two membranes can be identified as the capillary endothelium and an extracellular interstitium lumped with the peritoneal mesothelium.