Although a majority of studies indicate superior hemodynamic and clinical profiles of low osmolar compared with high osmolar contrast media, the effect of these agents on diastolic left ventricular function has not been examined. We prospectively examined hemodynamic, electrocardiographic, and echocardiographic indices of left ventricular function in patients undergoing contrast ventriculography with a high osmolar, ionic, monomeric contrast, diatrizoate (Renografin-76) compared with a low osmolar, ionic, dimeric contrast, ioxaglate (Hexabrix). Thirty patients were randomized to each group. There were no clinical differences between the two groups. The decrease in systemic pressures was significantly greater with diatrizoate after left ventriculography (-38.5 +/- 3.5 versus -18.2 +/- 2.3, p less than 0.001) and selective left coronary angiography (-29.5 +/- 2.4 versus -17.4 +/- 2.6, p less than 0.001). In addition, left ventricular end-diastolic pressure increased significantly more with diatrizoate (7.3 +/- 0.9 versus 2.7 +/- 0.8 mm Hg for ioxaglate, p less than 0.001). QT interval prolongation occurred in both patient groups. Diatrizoate decreased systemic vascular resistance, and increased cardiac output and left ventricular ejection fraction more than ioxaglate, while simultaneously increasing left ventricular end-diastolic volume and altering the peak atrial filling velocity. Negative dp/dt (p less than 0.05), but not Tau, computed by the logarithmic or derivative methods, was reduced by diatrizoate. These data indicate that significant alteration of diastolic filling patterns occurs with high osmolar compared with low osmolar contrast agents. Although the clinical significance of this observation is currently unknown, these data further support the reported hemodynamic superiority of the low osmolar, dimeric contrast agent ioxaglate during contrast angiography.