The Seville orange extract Citrus aurantium contains m-synephrine (phenylephrine) and octopamine; it causes cardiac disturbances in animals and is used by humans for weight loss. Juice from the orange (Seville orange juice [SOJ]) is used to "knock out" intestinal cytochrome P450 (CYP) 3A4 in bioavailability studies. The purpose of this study was to determine synephrine and octopamine concentrations in SOJ and SOJ's cardiovascular effects in normotensive humans. Subjects consumed 8 ounces of SOJ and water in crossover fashion followed by a repeat ingestion 8 hours later. Hemodynamic (heart rate; systolic, diastolic, and mean arterial pressure) measurements followed. Synephrine and octopamine were determined by high-performance liquid chromatography. Hemodynamics did not differ significantly between water and SOJ groups. Mean synephrine concentration of SOJ samples was 56.9 ± 0.52 μg/ml; octopamine was not detected. SOJ ingestion by normotensive subjects is expected to be safe. Individuals with severe hypertension, tachyarrhythmias, and narrow-angle glaucoma and monoamine oxidase inhibitor recipients should avoid SOJ consumption. Persons taking decongestant-containing cold preparations should also refrain from SOJ intake.