To investigate the nature of the variable response to inhaled histamine in monkeys, we performed dose-response curves in a group of 10 anesthetized Macaca mulatta monkeys before and after administration of propranolol and atropine in inhaled doses sufficient to produce significant beta-adrenergic and cholinergic blockade of airway smooth muscle. Animals were studied in a volume-displacement body plethysmograph and changes in pulmonary resistance (RL), dynamic compliance (Cdyn), frequency (f) and tidal volume (VT) were plotted against inhaled histamine concentration (0.016 to 64 mg/ml). Sensitivity to histamine was assessed by the concentrations producing a 50% increase in RL and a 50% decrease in Cdyn. A wide range of sensitivity (0.44 to 3.3 mg/ml for RL, 0.47 to 11.3 mg/ml for Cdyn) was found in this small group of animals, and this was not influenced by prior inhalation of propranolol. Atropine inhalation resulted in a marked decrease in sensitivity in all animals but did not reduce the variability of response.