The effect of a histamine releaser (48/80), an antigen (Ascaris suum extract) and of exogenous histamine infusion on antigen aerosol-induced bronchoconstriction was investigated in 24 mongrel dogs. During these substance infusions, the high values of arterial plasma histamine did not correlate with the degree of bronchoconstriction. Further, a severe bronchoconstriction with a relatively low arterial plasma histamine concentration was observed during antigen inhalation. During substance inhalation, a high local concentration of histamine is assumed to explain the increased bronchial ‘sensitivity’ to actual plasma levels of histamine. Also, the responsiveness of the bronchial tree to antigen aerosol was observed to be reduced 90 min after induction of a strong histamine release. The importance of histamine in the first phase of immediate hypersensitivity is discussed.