Positron emission tomography offers the ability to noninvasively assess regional myocardial perfusion in absolute terms (i.e., milliliters per gram per minute). Accurate estimates have been difficult to achieve with generator-produced Rb-82 because of the complex behavior of this tracer in the myocardium. The aim of the present study was to determine whether regional myocardial blood How could be assessed quantitatively with Rb-82 and positron emission tomography by using a two-compartment kinetic model. Regional perfusion in milliliters per gram per minute was estimated from dynamic tomographic scans after intravenous administration of Rb-82 in 18 studies in 13 intact dogs studied without intervention, after 2 and 24 hours of induced ischemia, during reperfusion after transient occlusion, or at rest and after pharmacological hyperemia after induced coronary artery stenosis. Regional flow was estimated along with the forward and backward rates of transport (k1 and k2 [minutes-1]) after the relative volume of distribution of the first compartment was fixed to 0.53 ml/ml and the tomographic parameters, the recovery and spillover fractions, were fixed to averaged values obtained in previous studies. In 36 comparisons, estimates of regional flow with Rb-82 correlated well with flow measured with concomitantly administered radiolabeled microspheres (r = 0.91, p < 0.05) over the How range from 0.14 to 4.25 ml/g/min. A putative index of viability, k2, increased significantly in regions with severe ischemia. The results suggest that quantification of regional myocardial perfusion is possible in centers using Rb-82 for estimates of myocardial perfusion when a physiologically appropriate, two-compartment model is used.