The current study evaluates the capacity of eugenol to regulate immediate allergic reaction by control of histamine release. Administrations of eugenol (1M/kg, i.p.) at 60 min b efore and 5, 10 min after the compound 48/80 treatment (8mg/kg, i.p.) were shown the mortality rates as 0, 44.4, and 77.8%, respectively. A 60 min before administered group revealed a significant inhibition of serum histamine release compared with those of 5 and 10 min after the compound 48/80 injection. Eugenol (6-48mM) was also showed a dose-dependent activity on the compound 48/80-induced histamine release from the highly purified population of Alcian Blue-positive peritonea] mast cells. These results indicate that in vitro treatment with exogenous eugenol inhibited the active response of mast cell populations and modulated its characteristics.