A technique for noninvasive determination of cardiac output by aid of first-pass radionuclide cardiography is described. After intravenous injection of 10-15 mCi technetium-99m-(99mTc) labeled red blood cells the method requires acquisition of a first passage time-activity curve recorded with a gamma camera over the left ventricle, the background corrected left ventricular count rate recorded after complete mixing of the tracer in the circulation, and determination of the distribution volume of the tracer. The method was applied in 14 patients with heart disease of various origins and evaluated against the conventional tracer dilution technique with arterial sampling of blood activity. Cardiac output determinations by external counting ranged from 2.30 to 8.56 l/min, mean +/- s.d. 4.50 +/- 1.66 l/min and by arterial blood sampling from 1.88 to 8.96 l/min, mean +/- s.d. 4.52 +/- 1.71 l/min. An excellent correlation was demonstrated between the two techniques, r = 0.978 (p less than 0.001). When no background subtraction was applied to the left ventricular counts at equilibrium, radionuclide cardiac output values were approximately 40% higher than those obtained by arterial sampling. The new first-pass radionuclide cardiographic technique may prove a useful tool in the noninvasive evaluation of cardiac function, especially in patients with arrhythmias and/or valvular incompetence.