We investigated the effect of vasodilation and flow rate on derived estimates of capillary permeability surface (PS) product and interstitial space size in the in situ canine heart. We used the multiple indicator dilution technique, with labeled red cells and albumin as reference tracers, Na ion as an interstitial space marker, and tritium-enriched water as a substance entering both interstitial and sarcomeric spaces. The simultaneous outflow curves for these substances were analyzed with a model of the coronary microcirculation which contained unique parameters representative of capillary and sarcolemmal PS products, the ratio of myocyte to interstitial space sizes and the heterogeneity of capillary transit times. Parameter optimization was accomplished by an efficient algorithm based on frequency-domain representations of the model and the data. Vasodilation at constant flow rate with decreased perfusion pressure in the heart working at a constant basal level had no significant effect on the permeability and space size parameters, but the capillary transit time heterogeneity was reduced. Restoration of control perfusion pressure by increased flow (in the face of continuing vasodilation) caused an increase in both capillary PS product and relative interstitial space size, but no change occurred in the sarcolemmal PS product. We conclude that there is no significant recruitment of myocardial cells with increased flow rate and that, when capillary recruitment occurs, it is only an effect of increased flow rate and unrelated to vasodilation per se. At high flow rates, with normal perfusion pressures, a mild but significant degree of interstitial edema accumulation is found.Circ Res 47: 312-328, 1980