The release of chemical mediators from sensitized cells is inhibited by drugs which increase intra-cellular cyclic adenosine monophosphate. Theophylline. which increases cyclic AMP through inhibition of phosphodiesterase, has been shown to inhibit mediator release in several in vitro systems. This study was undertaken to determine whether theophylline. as used for asthma therapy, would have this effect in vivo in humans. In three of six atopic subjects, inhibition of mediator release (as studied with the leucocyte hislamine release system) could be demonstrated after theophylline given orally in dosage commonly employed in asthma, This suggests that, in some asthmatic patients, theophylline may have beneficial effects other than bronchodilatalion.