The prolonged effect of barbiturates and inhalation anesthesia on airway response to histamine was studied in five groups of dogs. Group B (n = 10), H24 (n = 5), and H72 (n = 5) were anesthetized with sodium thiamylal (B) or halothane and N2O (H24, H72) for 3 h, during which a dose-response curve to histamine was obtained. The animals were then allowed to recover; 24 h (B and H24) or 72 h later, the animals were killed and anin vitrodose–response curve to histamine was obtained on a tracheal smooth muscle (TSM) specimen. Group C (n = 5), the control group, had no prolonged exposure to anesthesia. The dogs were immediately killed and thein vitrohistamine response of the TSM was measured. The results (mean ± SE) showed that the smooth muscle contractile properties (i.e., the maximum contraction to electrical field stimulation) were comparable in all four groups: 111 ± 12 g (B); 168 ± 23 g (H24); 106 ± 32 g (H72); and 107 ± 31 g (C). The maximum response (mean ± SE) to histamine (as % of maximum electrical contraction) was: 15 ± 6% (B), 30 ± 9% (H24), 32 ± 12% (H72), and 50 ± 8% (C). Statistical analysis of the data showed that the histamine response of Group B and Group H24 was significantly decreased compared to Group C (P< 0.01 and < 0.05, respectively); in Group H72 the results were not significantly different from Group C (0.1 >P> 0.05). To exclude the possibility that the diminution in histamine response was due to thein vivoexposure to histamine, a fifth group of animals served as sham. The animals were anesthetized with sodium thiamylal and killed 24 h later, having inhaled no histamine. The results obtained in this group were comparable with those obtained in Group B. The authors conclude that exposure to general anesthetics decreased airway smooth muscle sensitivity to histamine for at least 24 h after the cessation of anesthesia.