Phenothiazine (chlolpromazine, trifluoperazine, thioridazine, and fluphenazine) are potent inhibitors of the rapid uptake of adenosine by rat cerebral cortical synaptosomes. Other antipsychotics with fewer sedative side effects (clozapine, pimozide, haloperidol) were weaker inhibitors of adenosine uptake. It is hypothesized that inhibition of adenosine uptake is a significant factor in the sedative, antianxiety, and analgesic actions of the phenothiazines.