A noninvasive method for determination of cardiac output by aid of first passage radionuclide cardiography is presented. As opposed to most other scintigraphic methods, a forward blood flow is measured, even in patients with valvar incompetence. In addition, the technique allows measurement of cardiac output in the presence of cardiac arrhythmias. No geometrical assumptions, corrections for radiation attenuation, loss of tracer, or empirical correction factors due to extracardiac radioactivity are required. We have evaluated the method in 19 patients with various heart diseases by comparison of the radionuclide cardiac outputs with those derived from the thermodilution technique performed simultaneously. Eight patients had valvar incompetence and 2 had cardiac arrhythmias. The mean radionuclide and thermodilution cardiac output values were 5.03 l/min (SD 1.21) and 5.18 l/min (SD 1.09), respectively. The 95% confidence interval for the bias was -0.40 to 0.10 l/min, and correlation analysis demonstrated an excellent correlation between results obtained with the two methods, r = 0.91 (P < 0.001). This study shows that the improved gamma camera method represents a valid noninvasive technique for determination of cardiac output.