Six patients with active extrinsic bronchial asthma showed a diminished leucocyte adenyl cyclase response to isoproterenol whereas seven patients in remission showed a significant increase in cyclic AMP when their cells were stimulated with isoproterenol. A significant difference in the control (basal) values of leucocyte adenyl cyclase activity between the patients with active asthma and those in remission suggests that in the active phase of asthma beta adrenergic receptors are maximally stimulated by circulating endogenous catecholamines and further stimulation with sympathomimetic amines becomes increasingly difficult. In this situation, the minor alpha receptor stimulating effect of adrenaline may become dominant and cause adrenaline reversal which is commonly observed in status asthmaticus. The leucocyte adenyl cyclase activity and its responsiveness to catecholamines did not relate to airways response induced by beta blockade or allergen challenge, nor was there any correlation between the activity of this enzyme and the total circulating reagins. These results together with the observations of reduced metabolic responses to adrenaline administration in patients with severe degree of asthma suggest that the reduced beta receptor function in asthma may reflect a failing counter-regulatory mechanism rather than be considered the cause of bronchial hyper-reactivity and atopic state in asthma. The airways response to beta blockade and allergen challenge depends on the initial or basal bronchomolor lone. The differing airways response to beta blockade in patients with extrinsic bronchial asthma and chronic bronchitis may be of clinical importance in classifying patients with obstructive airways disease.