Increased 3H-spiperone binding after chronic neuroleptic treatment has been proposed as a molecular model of tardive dyskinesia. Sulpiride has been claimed to be an atypical neuroleptic that might not produce tardive dyskinesia. The effect of chronic sulpiride was, therefore, compared to that of chronic haloperidol on striatal 3H-spiperone binding. 3 weeks of haloperidol feeding caused a 28% increase in 3H-spiperone binding, whereas even very high dose sulpiride had no effect on spiperone binding. These findings support the concept that sulpiride may be a unique neuroleptic with regard to long-term effects on dopamine receptors.