A representative phosphodiesterase inhibitor, theophylline, and an orally active adenyl cyclase stimulator, salbutamol, were tested for their ability to inhibit the dermal allergic reaction of rhesus monkeys to Ascaris antigens. Salbutamol was also tested for in vitro inhibition of the allergic histamine release from human leukocytes. Salbutamol inhibited the first stage histamine release reaction at concentrations of 10––5 to 10––6 M and in vivo inhibited the Ascaris skin reaction 42% when given orally once, 1 h before skin testing. Theophylline at 12 mg/ kg given similarly inhibited the Ascaris reaction 94%. Neither agent inhibited the skin reaction induced by 10 μg of histamine. Anti-histamines inhibited the histamine reaction without a significant effect on the Ascaris titer. Drug effects in vivo were quantitated by comparing the Ascaris titer of groups of animals on the day of treatment with the titers of the same animals 2–4 weeks before and after treatment. The change in sensitivity induced by multiple challenges was controlled by comparison with the titers of untreated monkeys tested at all intervals. The results indicate that agents which stimulate cellular levels of cAMP and prevent allergic histamine release in vitro also prevent allergic histamine release in vivo.