The purpose of this project is to investigate cyclic nucleotide metabolism as correlated with normal and abnormal function in pulmonary tissue. Mice sensitized to histamine by the use of Bordetella pertussis vaccine will serve as the laboratory model of the atopic abnormality. Studies will employ whole lung tissue initially with emphasis being directed toward preparations of bronchial smooth muscle. The objectives are to investigate the role of cyclic AMP and cyclic GMP in the sensitized state, particularly in response to histamine challenge. Studies will be aimed at explaining abnormal alterations in these two nucleotides by examining the enzymes concerned with their synthesis and degradation. Methods employed will include radioimmunoassay, protein binding, and enzymatic flourometric techniques.