A study was undertaken to identify the most accurate 99mTc-labeled radiopharmaceutical and to determine the accuracy of a noninvasive radionuclide technique (antecubital injection and precordial detection) for cardiac output determinations. Phase I employed sodium pertechnetate, stannous pyrophosphate with sodium pertechnetate, technetium-99m red blood cells, and technetium-99m human serum albumin as radionuclide tracers. Cardiac output was determined by the dye dilution method and then by the invasive radionuclide technique. The radiopharmaceutical was injected into the same intracardiac catheter used in the dye dilution method. Seven to 10 mongrel dogs were used to test the accuracy of each radiopharmaceutical. A paired t test and regression analysis indicated that technetium-99m human serum albumin was the most accurate radiopharmaceutical for cardiac output determinations, and the results compared favorably to those obtained by the dye dilution method. In Phase II, technetium-99m human serum albumin was used as the radionuclide tracer for cardiac output determinations with the noninvasive technique. The results compared favorably to those obtained by the dye dilution method. Regression analysis indicated a correlation coefficient of 0.91. A paired t test demonstrated that the difference between the two methods was not statistically significant (p greater than 0.05). The data suggest that a noninvasive radionuclide technique using cardiac output determinations in humans.