membranes to 190±10 fmol/mg protein in treated membranes (P = 0.01). These data indicate that the adenosine receptor antagonist, caffeine, induces a compensatory sensitization of the Al receptor-adenylate cyclase system and downregulation of jBadrenergic receptors, and provides a molecular mechanism for the caffeine withdrawal syndrome. IntroductionThe daily consumption of caffeine is estimated at 200 mg per adult (1, 2), approximately equivalent to two cups of coffee/d. Acute caffeine intake is associated with arrhythmias (3), increased heart rate (4, 5) and stroke volume (6), altered blood pressure (5), sleeplessness (7), and other physiologic and behavioral alterations. The physiologic and metabolic effects of chronic caffeine use are less well-documented (8-1 1) and little is known about the biochemical effects of chronic caffeine ingestion.Although the pharmacologic action of the methylxanthines Address reprint requests to Dr. Stiles,