A clinically significant interaction between epinephrine or levonordefrin with nonselective beta-adrenergic blocking agents, although apparently rare in the dental setting, is potentially serious and can lead to significant hypertension with a concomitant reflex bradycardia. Based on the results of epinephrine infusion studies, the severity of the interaction seems dose related; small epinephrine doses cause less of a pressor response than larger doses. The interaction can be seen after intraoral submucosal injections but is generally of a smaller magnitude, at least with only 1 or 2 cartridges of lidocaine plus 1:100,000 epinephrine. However as demonstrated by 1 case report, some individuals are hypersensitive to this interaction. Inadvertent intravascular injections of local anesthetic plus vasoconstrictor and the use of high doses of vasoconstrictor are likely to result in a more pronounced response. Patients with significant cardiovascular disease may be especially vulnerable to the most serious sequelae resulting from the pressor reactions of the drug combination.