Assessment of the functional significance of anatomically defined coronary stenoses has been hampered by the lack of clinically applicable techniques of measuring coronary blood flow or flow ratios. A digital angiographic technique is reported that allows rapid analysis of relative regional coronary blood flow during routine cardiac catheterization. This technique was validated in dogs by comparing digital flow ratio estimates with electromagnetic-flow (EMF) ratio measurements. Fourteen open-chest dogs had EMF probes placed on the proximal left anterior descending artery before selective coronary angiography. Electrocardiographically gated images were acquired directly by a digital radiographic system during both baseline blood flow and either contrast or papaverine-induced hyperemia. Dual-parameter functional images were generated using color and intensity coding to represent contrast arrival time and contrast density, respectively. For analysis, myocardial areas of interest were created over the distal perfusion bed of the left anterior descending coronary artery. Mean contrast density/appearance time (CD/AT) values were computer calculated as the mean density divided by the mean arrival time for each. Coronary flow reserve was determined as the ratio of the CD/AT value for a hyperemic image divided by the CD/AT value for the corresponding baseline image. CD/AT ratios correlated well (r = 0.92) with actual EMF ratios (CD/AT Ratio = 0.90 EMF Ratio +0.12, n = 48 ratios). Reproducibility was +/- 13%. Interobserver (r = 0.99) and intraobserver (r = 0.98) variability was excellent. Thus, rapid, accurate and reproducible estimates of relative regional coronary blood flow are possible using digital radiography.