Purpose: The intravenous or intramuscular administration of epinephrine is recommended treatment in systemic anaphylaxis. The goal was to evaluate epinephrine plasma levels after intramuscular injection into the buccinator muscle in comparison to inhaled epinephrine. Methods: In this pilot study in humans, we measured plasma epinephrine concentrations before and after epinephrine administration by intramuscular injection, or by inhalation, with intramuscular saline and intravenous epinephrine as the negative and positive controls, respectively. Results: Peak plasma epinephrine concentrations were higher after epinephrine was injected intramuscularly with a maximum plasma epinephrine concentration of 3367.2 pg/ml. After administration by inhalation epinephrine peak level was 151.89 pg/ml. Conclusions: In cases of respiratory distress when anaphylaxis is a possible cause, at first the application of epinephrine by inhalation may be of value. Manifest major cardiovascular reactions according to anaphylaxis without availability of a venous access can only be treated by titration of epinephrine intramuscularly. The buccinator muscle is a useful site for dentists involved on treatment of anaphylaxis.