SUMMARY. The effects of metabolic coronary vasodilation on transcapillary exchange in the heart were examined in anesthetized dogs by use of the multiple indicator dilution technique. Animals were studied under basal conditions and during coronary sinus pacing. To obviate adrenal medullary stimulation, catheters were placed in coronary artery and coronary sinus in a closed chest preparation. Plasma catecholamine concentrations were determined to provide an index of the level of sympathetic tone. Labeled albumin and sucrose were injected into the coronary artery, and outflow dilution curves were secured. Analysis of these, with a model incorporating throughput and returning components, and heterogeneity of capillary transit times, provided parameters reflecting flow, permeability-surface product for sucrose, and capillary heterogeneity. Coronary sinus pacing increased both heart rate and plasma norepinephrine values; in response, myocardial oxygen consumption increased, metabolic vasodilation occurred, and coronary flow increased. The capillary permeability-surface product for sucrose increased with the flow but tended to plateau at higher values, showing a saturation phenomenon. Capillary heterogeneity, present in control animals with low sympathetic tone, was grossly decreased during cardiac metabolic activation. The Crone-Renkin approximation formula for the permeabilitysurface product yielded values that were too low at low flows and values approaching those from the complete model at high flows. The findings indicate an integrated pattern of circulatory response to cardiac metabolic activation characterized by decreased resistance, increased flow, increased permeability-surface product, and reduced heterogeneity. The last two effects amplify the capacity of increased flow to deliver substrates to heart muscle cells. (Circ Res 53: 719-730, 1983) AN elevation in coronary blood flow during cardiac metabolic stimulation represents the expected response of the coronary circulation to the increased myocardial demand for oxygen and nutrients. Measurement of coronary blood flow does not, however, provide a complete reflection of the ability of the heart to provide for its nutritional requirements. The exchange capability of the capillary system (its permeability-surface product), in particular, is an important variable modulating the effect of changes in flow-it controls the exchange of substrates between the vascular compartment and the extracellular space of the heart, where they are presented to the myocardial cells. An increase in the capillary permeability-surface product would magnify the effectiveness of a higher coronary flow for the delivery of nutrients to the interstitial space of the heart, as would a decrease in capillary heterogeneity. In the present work, it is our purpose to characterize whether, and to what degree, these occur.We previously examined the relation between coronary flow and the permeability-surface product for sodium in the working canine heart with the multiple indicator dilution ...