Chronic treatment of rats with neuroleptics results in elevated numbers of dopamine D2-like receptors. The present study was done to determine whether neuroleptics altered the density of one type of dopamine D2-like receptors, namely the dopamine D4 receptor. We here describe the effect of a one-month treatment with haloperidol on dopamine D4 receptor mRNA and protein levels in rat striatum. Endogenous levels of dopamine D4 receptor mRNA in rat striatum are very low and, therefore, reverse transcription and subsequent amplification were used for quantification. Dopamine D4 receptor density was, because of the absence of a dopamine D4 receptor specific [3H]ligand, determined by the difference between the number of binding sites for [3H]nemonapride and [3H]raclopride. Scatchard analysis of [3H]nemonapride and [3H]raclopride binding show that treatment for one month with halperidol elevates the density of dopamine D4 receptors in rat striatum by approximately 2-fold, whereas dopamine D2 and D3 receptors together show a 19% higher receptor density. Dopamine D4 receptor mRNA was also approximately increased by 2-fold.