In order to obtain a functional estimate of the diffusional capacity of the myocardial capillary bed, the permeability surface area product (PS) for Cr‐EDTA (mol. wt = 341) and cyanocobalamine (vitamin B12, mol. wt = 135) was determined in spontaneously beating Langendorff‐perfused rat hearts over a wide range of coronary flow rates (700–3000 ml min‐1100 g‐l). PS was determined by a single injection, colorimetric indicator dilution technique, allowing multiple, rapid and accurate determinations to be made in the same heart. During maximal vasodilation with nitroprusside Na PS averaged 535 ± 33 and 220 ± 22 ml min‐1100 g‐1for Cr‐EDTA and vitamin B12respectively at the highest flow (2917 ±74 ml min‐1100 g‐1). The vasculature of the heart was found to be highly hererogeneous, since PS increased with flow and there were marked variations of extraction over transit times. A functional estimate of ‘equivalent pore radius’ was obtained from the ratio PSCr.EDTA/PSB12, which was 2.61 ± 0.15 demonstratiag a marked restriction to diffusion corresponding to a pore radius of 51 (41–75) Å. This value is similar to that from skeletal muscle determined by the same method while PS‐values are 40–45 times higher in the heart (Haraldsson&Rippe 1986). Taken together with morphological estimations of capillary surface area and endothelial path depth, these data indicate a 3‐fold increase in the density of pores available for diffusion in the myo