Adenosine has sedative properties, and adenosine-receptor agonists have been found to reduce anesthetic requirements in rodents. This study determined whether adenosine, in hypotensive doses, reduces anesthetic requirements in halothane-anesthetized dogs. In seven animals, minimum alveolar concentration (MAC) for halothane was determined by a tail-clamp technique at three time points: after 2 h of halothane anesthesia, during adenosine-induced hypotension (mean arterial pressure: 55 mmHg), and 1 h after adenosine was discontinued. In other dogs, the effects of aminophylline, dipyridamole, or the specific adenosine-receptor antagonist 8-phenyl-theophylline (8-PT) on the halothane-adenosine interaction were studied. Adenosine significantly reduced halothane MAC, by 49%, from 0.76 ± 0.05 to 0.39 ± 0.05 vol% (mean ± SEM). This effect was blocked by the concurrent administration of aminophylline (n = 5,P< 0.05) or 8-PT (n = 4 of 4). When dipyridamole, which increases the plasma concentrations of endogenous adenosine, was administered alone, halothane MAC was reduced from 0.79 ± 0.03 to 0.67 ± 0.05 vol% (n = 5,P= 0.09). We conclude that exogenous adenosine substantially reduces halothane MAC in dogs and that this effect is blocked by the concurrent administration of the adenosine-receptor antagonists aminophylline or 8-PT. Relatively small alterations of endogenous adenosine concentrations, however, do not substantially reduce halothane MAC.