Diffusional permeability (P) to inulin (P-in), albumin (P-alb), and dextrans [70 (P-dx 70), 150 (P-dx 150), 550 (P-dx 550), and 2,000 (P-dx 2,P-000)] was determined in specimens of parietal pericardium of rabbits, which may be obtained with less damage than pleura. P-in, P-alb, P-dx 70, P-dx 150, P-dx 550, and P-dx 2,P-000 were 0.51 +/- 0.06 (SE), 0.18 +/- 0.03, 0.097 +/- 0.021, 0. 047 +/- 0.011, 0.025 +/- 0.004, and 0.021 +/- 0.005 x 10(-5) cm/s, respectively. P-in, P-alb, and P-dx 70 of connective tissue, obtained after removal of mesothelium from specimens, were 10.3 +/- 1.42, 2.97 +/- 0.38, and 2.31 +/- 0.16 x 10(-5) cm/s, respectively. Hence, P-in, P-alb and P-dx 70 of mesothelium were 0.54, 0.20, and 0.10 x 10(-5) cm/s, respectively. Inulin (like small solutes) fitted the relationship P-solute radius for restricted diffusion with a 6-nm "pore" radius, whereas macromolecules were much above it. Hence, macromolecule transfer mainly occurs through "large pores" and/or transcytosis. In line with this, the addition of phospholipids on the luminal side (which decreases pore radius to similar to1.5 nm) halved P-in but did not change P-alb and P-dx 70. P-in is roughly similar in mesothelium and capillary endothelium, whereas P to macromolecules is greater in mesothelium. The albumin diffusion coefficient through connective tissue was 17% of that in water. Mesothelium provides 92% of resistance to albumin diffusion through the pericardium.