A nongeometric, attenuation-corrected technique to quantitate left ventricular volumes using equilibrium radionuclide angiography was validated in vitro and in vivo. In vitro experiments were performed to derive a linear attenuation coefficient, which was then employed in the volume determinations using balloons in a water bath. Good in vitro correlation was found between radionuclide and actual volumes (r = 0.99, p less than 0.0001), over a wide range (5 to 400 ml). In vivo validation was done by comparing the nuclear technique to contrast angiography in 29 patients: Good correlations were found for end-diastolic volume (r = 0.98), end-systolic volume (r = 0.95), stroke volume (r = 0.96), and ejection fraction (r = 0.85). When the conventional linear attenuation coefficient was used, the radionuclide technique consistently overestimated volumes in vitro and in vivo. Although high intraobserver and interobserver correlation coefficients were found (r from 0.88 to 0.93), significant individual variability existed, particularly in the interobserver data. Our data provide unique validation of radionuclide volume determinations, using an experimentally determined attenuation coefficient, which results in improved accuracy.