A powerful, simple model has been developed for measuring regional blood flow using first-pass tracer kinetics with external detectors such as fast positron emission tomographs (PET). Its derivation is based on the hypothesis that during the first transit of a bolus of activity through an organ there exists a period during which the tracer has not left the region of interest, so that the venous concentration of the tracer is zero. Provided that this condition is met, measurement of blood flow can be obtained in any organ with any radiotracer since there are no requirements in the derivation of the model for diffusion or extraction characteristics of the tracer. The general model has been demonstrated for a special case in the heart using intravenous bolus injections of rubidium-82 with regional positron detectors (beta probes) and validated by comparison with independently determined for by labeled microspheres over a wide range of flow values from zero to five times normal resting coronary blood flow.