The effects of some adenosine agonists and calcium channel antagonists on the induction of tolerance to and dependence on barbital in mice have been studied. The concurrent administration of barbital and one of the following adenosine agonists, D- or L-phenylisopropyl adenosine, cyclopentyl adenosine and chloroadenosine, or the adenosine antagonists theophylline or 8-phenyltheophylline did not change the intensities of tolerance to and dependence on the barbiturate. N-ethylcarboxamide adenosine administered during the period of chronic administration of barbital significantly reduced the withdrawal syndrome. The administration of the calcium channel antagonists diltiazem, verapamil or nifedipine was also ineffective in altering the processes of tolerance and physical dependence when given concomitantly with barbital. Abstinence behavior was significantly reduced when mice were treated during the first 48 h of withdrawal from the barbiturate with either L-phenylisopropyl adenosine, N-ethylcarboxamide adenosine, nifedipine or verapamil. These results are discussed in relation to the attenuation of tolerance to and dependence on benzodiazepines induced by similar treatments.