Available data indicate that patients with bronchial asthma are relatively unresponsive to the systemic effects of epinephrine, exhibiting less marked changes in pulse rate, blood glucose levels and serum glycerol and nonesterified fatty acid concentrations than normal subjects. Previous work from this laboratory indicates that mixed peripheral blood leukocytes from patients with asthma are similarly hyporesponsive in terms of alterations in cyclic AMP concentrations in the presence of isoproterenol. Using the peripheral blood leukocyte system as a model, a detailed examination of the adenyl cyclase system of asthmatic patients will be made asking the following questions: 1) Is the decreased cyclic AMP response due to decreased formation or increased destruction of cyclic AMP? 2) Is the decreased responsiveness inborn or acquired? 3) Does treatment of normal adults with catecholamines over an extended period alter responsiveness? 4) Do patients with intermittent intrinsic asthma exhibit acute alterations in responsiveness secondary to infection? 5) Do prostaglandins and corticosteroids alter or circumvent the hyporesponsiveness? 6) Do relatives of patients with asthma exhibit similar alterations in responsiveness? With a better understanding of the nature of the alteration in catecholamine responsiveness in patients with asthma more effective approaches to therapy should be possible.