Histamine aerosol was administered to 10 anesthetized paralyzed artificially ventilated dogs whose vagi were first intact, then cut, and then peripherally stimulated. Pulmonary resistance (RL) was measured and dose-response curves determined in the three conditions. The dogs were divided into two groups based on the initial response to histamine with the vagi intact. The low-dose (LD) group had a greater than or equal to 50% increase in RL when exposed to a histamine concentration of 1.0 mg/ml. The high-dose (HD) group had a greater than or equal to 50% increase in RL when exposed to an aerosol containing 3.0 mg/ml histamine or more. In both groups there was a dose-related increase in RL with histamine with the vagi intact, cut, or stimulated. In three of the LD dogs there was a greater than additive interaction between vagal stimulation and inhaled histamine, whereas in the HD dogs the interaction was at most additive. With the vagi cut, both groups had a significantly lesser histamine response. The results show that differences in histamine responsiveness between dogs is in part related to varying degrees of nonreflex histamine-vagal interaction.