Rapid measurements of coronary vascular volume are necessary for a complete understanding of phasic coronary flow. Because no standard method is capable of making these measurements, we developed a method that uses digital subtraction angiography to image an intravascular contrast agent. The method is capable of measuring vascular volume in 33 ms and can be repeated three times per second. The method was first validated in phantoms. We then used this method to measure coronary vascular volume in the isolated, perfluorochemical-perfused, interventricular canine septum. The speed of the measurements allowed us, for the first time, to directly measure transients in vascular volume following sudden changes in perfusion pressure. At the steady-state and maximal vasodilation, coronary vascular volume varied from 7.5 +/- 1.2 (SE) ml/100 g at a perfusion pressure of 20 mmHg to 12.1 +/- 1.9 ml/100 g at 90 mmHg, which is similar to other reports. After a sudden change of 40 mmHg in perfusion pressure, vascular volume changed with a time constant of 3.2 +/- 0.3 (SE) s. Increasing ventricular wall stretch had no effect on either the steady-state volumes (P = 0.25) or the time constant for volume changes (P = 0.17). The fact that the time constant is longer than the cardiac cycle, yet much shorter than the time necessary to measure vascular volume using other methods, highlights the need for rapid measurements of vascular volume.