High-dose dobutamine used in dobutamine stress echocardiography (DSE) has hemodynamically based side effects due to a variable combination of beta1 (inotropic) and beta2 (vasodilator) effects. Of concern is the development of an "empty ventricle syndrome" associated with intracavitary or outflow tract obstruction and resultant symptomatic hypotension. This study was undertaken to determine whether the concurrent administration of normal saline (N/S) would decrease symptoms, limit the development of left ventricular outflow tract (LVOT) obstruction and hypotension by maintaining left ventricular volume. One hundred patients, mean age 66 years +/- 12, presenting for a DSE were randomized into two groups. One group (n = 50) received N/S at a rate of 800 ml/hour during the test, the second group received dobutamine alone. Patients were instructed to report and quantify symptoms on a scale of 1 to 10. Echocardiographic measurements of end systolic volume (ESV) and LVOT gradients were taken prior to dobutamine and at peak dose. There was no difference in symptom scores (3.5 +/- 5.1(N/S) vs. 3.0 +/- 4.7, P = 0.6), change in systolic blood pressure (BP) (-0.74 mmHg +/- 33 (N/S) vs. -0.89 +/- 35, P = 0.9) maximum LVOT gradient at peak (16.4 mmHg +/- 16.1 (N/S) vs. 13.9 mmHg +/- 9, P = 0.4), or ESV at peak (17.9 mL +/- 13.4 (N/S) vs. 15.5 ml +/- 10.6, P = 0.37). Furthermore, there was no difference in the number of patients (10/50 (20%) in both groups) who developed a significant LVOT gradient, defined as greater than 20 mmHg at peak dose. Despite the sound theoretical basis of N/S infusion to protect against "empty ventricle syndrome" during DSE this randomized trial does not demonstrate any symptomatic or hemodynamic benefit.