A problem in accurately measuring regional myocardial blood flow by radiation washout techniques is the inability to localize precisely the origin of radiation in tissue. We developed a new approach for in vivo localization and quantification of regional blood flow. A miniature, silicon, solid-state, avalanche radiation detector, which measures the low-penetrating radiation from commonly available radionuclides, was constructed. Low-penetrating radiation has a limited range in tissue, and by selecting appropriate tracers, we vary the volume that our probe detects. The volume of the heart monitored by the avalanche probe ranges from less than 0.01 to 1 cm3, depending on the radionuclide used and the collimator design. In open-chest dogs, 2-5 mCi of xenon-133 dissolved in saline were injected into coronary arteries and the probe was placed over regions of interest to measure regional myocardial blood flow by the Kety-Schmidt formula. Detection of xenon-133 decreased as an exponential function of distance, with less than 10% of radioactivity detected at 0.6 cm away from the radiation source. The measured detection volume for xenon-133 was approximated at 0.5 cm3. Measurements of regional blood flow with the probe correlated closely to epicardial flow measured with radioactive microspheres (r= 0.88 ± 0.04 [SDI) in five dogs, and to proximal coronary flow measured with electromagnetic meters (r= 0.87 ± 0.05) in five dogs. Repetitive measurements during stable hemodynamics were reproducible. Thus, with avalanche detectors we obtained reliable and valid in vivo measurements of myocardial blood flow from small volumes.