The comparative timing of hemodynamic alterations by sublingual nitroglycerin administered by spray vs. tablet has not been studied. Similarly, the directly measured comparative effects on left ventricular pressures have not been reported. To investigate these issues, we analyzed 49 patients undergoing elective diagnostic cardiac catheterization who were randomized to receive 0.4 mg sublingual nitroglycerin by either spray or tablet. Before administration of contrast medium, control determinations of left ventricular end-diastolic and systolic pressures and heart rate were done. These parameters were then evaluated at half-minute intervals for 5 min. Left ventricular end-diastolic pressure was reduced similarly in both groups, with the reduction achieving significance at 1.5 min in the spray and 2.0 min in the tablet group. Lowering of the left ventricular systolic pressure was also similar in the two groups, reaching significance at 2.5 min with spray and 2.0 min with tablet. Heart rate increased significantly by 2.0 min in the tablet group but did not change in the spray group. These findings were not altered by the level of resting left ventricular end-diastolic pressure or use of chronic nitrates. Thus, we found nitroglycerin to be similarly effective in timing and extent of response whether administered by spray or tablet, though the difference in heart rate responses remains unexplained.