We investigated the effect of aqueous extract of Perilla frutescens (Labiatae) (PFAE) on the mast cell-mediated immediate-type allergic reactions. PFAE (0.05 to 1 g/kg) dose-dependently inhibited systemic allergic reaction induced by compound 48/80 in rats. PFAE (0.1 and 1 g/kg) also significantly inhibited local allergic reaction activated by anti-DNP IgE. When PFAE was pretreated at the same concentrations with systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. PFAE (10(-3) to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, When PFAE (1 mg/ml) was added, transiently and significantly increased about 4-fold compared with that of basal cells. Moreover, PFAE (0.001 and 0.01 mg/ml) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production. These results indicate that PFAE inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.