Cyclic AMP levels and adenylate cyclase and phosphodiesterase activities were measured in control and ovalbumin-sensitized guinea pig lungs. Cyclic AMP levels were raised by epinephrine (0.01-10 mug/ml) in both control and sensitized lungs; the response being larger in the former group. Epinephrine (10(-9) -10(-6) M) stimulated adenylate cyclase in sensitized but had only a minimal effect in control preparations. Phosphodiesterase activities were equal in both groups. The hypersensitivity of adenylate cyclase response to epinephrine concurrent with diminished accumulation of cyclic AMP in sensitized guinea pigs indicate that antigen sensitization alters the response of the cyclic AMP system to epinephrine.