Histamine, an important inflammatory mediator in allergic diseases and asthma, has been reported to have modulator effects on T cells, suggesting that the bronchial microenvironment may regulate the function of resident T cells. We examined the effect of histamine on the release of the Th2‐associated cytokines IL‐4 and IL‐5 and the Th1‐associated cytokine IFN‐γ by 30 CD4⁺ T cell clones from peripheral blood or bronchial biopsy of one atopic subject. Based on the IL‐4/IFN‐γ ratio, the clones were ascribed to the Th2 (ratio >1), Th0 (ratio  0.1 and 1) or Th1 (ratio <0.1) phenotype. Histamine inhibited IFN‐γ production by Th1‐like cells (P<0.02, Kruskall–Wallis), especially from bronchial biopsy, but had no effect on IL‐4 release. Regarding Th0 clones, histamine inhibited IL‐4 production (P<0.02) in a dose‐dependent manner and slightly inhibited IFN‐γ production, but had no effect on Th2‐like cells. Histamine had a heterogeneous and insignificant effect on IL‐5 production. The H₂‐receptor antagonist ranitidine completely reversed the inhibition of IL‐4 and IFN‐γ production, whereas the agonist dimaprit mimicked this effect. In contrast, H₁‐ and H₃‐receptor agonists and antagonists had no significant effect. These data demonstrate that histamine has different effects on IL‐4 and IFN‐γ release by T helper cells according to their phenotype via H₂‐receptors. This study extends the immunomodulatory effects of histamine which may contribute to the perpetuation of airway inflammation in asthma.