In this study the possible antagonistic effects of five different antipsychotics on the discriminative stimulus properties of 10 mg/kg cocaine were evaluated by use of a two-lever food-reinforced drug discrimination procedure in rats. To do so, rats were treated with several doses of haloperidol, risperidone, seroquel, sertindole, and olanzapine, either at 60 or 120 min prior to testing. With all compounds tested, no substantial antagonism of the cocaine cue was observed. Only with haloperidol (maximum 60%), risperidone (maximal 20%), and olanzapine (maximal 20%) a partial antagonism without clearcut dose-response was observed. Clozapine, seroquel, and sertindole did not influence the discriminative stimulus properties of cocaine. These results indicate that antipsychotics with different pharmacological profiles are unable to antagonize more than partially the cueing properties of 10 mg/kg cocaine in rats, pointing to the unique underlying stimulus properties of this stimulant.