Left ventricular (LV) volumes are important prognostic indices in patients with heart disease. Although several methods can evaluate LV volumes, most have important intrinsic limitations. Real-time three-dimensional echocardiography (RT3D echo) is a novel technique capable of instantaneous acquisition of volumetric images. This study was undertaken to validate rapid LV volume calculations with RT3D echo and to determine their usefulness in cardiac patients. Initially, we reported the results obtained in 25 patients. During the course of these studies, it was apparent that an important number of patients had suboptimal endocardial border definition to allow for reliable volume calculation. We therefore decided to modify the protocol to include the injection of EchoGen, a contrast agent for intravenous injection that opacifies the left ventricular cavity and thus enhances endocardial border resolution. We have studied 90 patients with contrast injection that have yielded 75 evaluable patients. LV volume measurements ranged from 25 to 408 ml (mean 106+/-64 ml) by RT3D echo and from 17 to 532ml (mean 103+/-72) by MRI. There was a strong correlation between the RT3D and MRI measurements (r=0.92, mean difference 3+/-28 ml). There was strong inter-observer agreement for the measurement of end-diastolic and end-systolic volumes (r=0.96, mean difference -3+/-20 and r=0.98, mean difference 1+/-12, respectively). There was also a strong correlation between the contrast-enhanced RT3D echo and MRI measurements of LV volumes (r=0.95). The difference between RT3D echo-derived measurements and MRI-derived measurements was significantly smaller after contrast enhancement (3+/-28 ml baseline to -2+/-23 ml contrast, p=0.04). When the difference in measurements between the two techniques was analyzed as a percentage of the MRI volume, there was a significant improvement in the contrast-enhanced measurements (%difference 14%+/-38% at baseline, 4%+/-27% with contrast, p=.00005). Thus, in an unselected population of cardiac patients, RT3D echo accurately predicts MRI-derive LV volumes. Contrast enhacement improves endocardial border definition and reduces the error in LV volume calculations.