The effect of Ephedrae herba (Mao) on histamine content was investigated. When rat basophilic leukemia (RBL-2H3) cells were incubated for 48 h with Mao, Mao decreased histamine content in a concentration-dependent manner. However, the ratio of released histamine to total histamine was scarcely affected by Mao treatment when RBL-2H3 cells were stimulated by ionomycin. On the other hand, the content of β-hexosaminidase, another marker of degranulation, was only slightly decreased by Mao. The expression level of the active form (53 kDa) of L-histidine decarboxylase, the enzyme which synthesizes histamine, was partially suppressed by Mao. Furthermore, Mao significantly suppressed proliferation of RBL-2H3 cells in a concentration-dependent manner. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine revealed an increasing effect of Mao on cAMP level in RBL-2H3 cells. Since this result suggested that Mao may stimulate adenylate cyclase, we evaluated the effect of adenylate cyclase inhibitor SQ 22536 on Mao-induced decrease in histamine content. As a result, we showed that SQ 22536 did not have a reducing effect of Mao. From these results it is understood that Mao decreased histamine content by inhibiting cell proliferation and expression of histidine decarboxylase. However, these effects are not related to the increase in cAMP.