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Recommendations for head-up tilt testing (HUT) often include the prolonged abstaining from food and water consumption (nothing by mouth [NPO]) and intravenous fluids administration before HUT. After the baseline test, supine equilibration periods are recommended before and between each dose of medication. The aim of this study was to determine if similar results are obtainable with a simpler protocol. After 2-3 hours NPO, 1,540 HUTs were performed at 70 degrees for 30 minutes unless predetermined endpoints were reached. Then, with the patient remaining in the tilted position, isoproterenol (ISO) (1 microgram/min), titrated every 3 minutes to a maximum of 5 micrograms/min (n = 803 patients), sublingual nitroglycerin (NTG) (300-400 micrograms) (n = 143 patients), or edrophonium (EDP) (5 mg) repeated once after 3 minutes (n = 46 patients) were administered. No aspiration or other adverse effects attributable to the abbreviated fasting period were observed. ISO was well tolerated as doses were increased. Vasovagal manifestations developed in 31% of ISO tests, in 11% with EDP, and in 50% with NTG (P < 0.001). Time consumed with rehydration before and postural changes during HUTs may be avoided when ISO is administered. With NTG the response may be excessive.