Conventional radionuclide techniques are limited by their inability to deliver noninvasively a compact bolus of radionuclide indicator into the left heart. This can be accomplished by the inhalation of oxygen-15-labeled carbon dioxide. The inhaled carbon dioxide passes freely across the alveolar membrane and enters the carbonate cycle, which, under the accelerating influence of carbonic anhydrase, transfers the oxygen-15 tracer onto water in the pulmonary venous blood. The result is an abrupt tracer delivery to the pulmonary venous system with subsequent tracer input to the left heart at a rate limited only by the pulmonary blood flow. These properties of oxygen-15-labeled carbon dioxide have been used to develop a specialized indicator-dilution method for quantitation of left-to-right cardiac shunt flow. The results agree well with those obtained by oxymetry at cardiac catheterization. In clinical application, the ease and reliability of this technique are remarkable. Its use is presently limited to clinical facilities with the capability for on-line production of the short-lived gases. The techniques provide a good example of the utilization of biologically active radiopharmaceuticals and are a potentially useful source of information about the hemodynamic properties of the central circulatory system.