Intracerebroventricular infusion of an all-phosphorothioate antisense oligodeoxynucleotide targeted at the rat dopamine D3 receptor mRNA (10 micrograms h-1, 5 days) resulted in a significant reduction (19%) of the binding of the [D2 + D3] ligand [3H]spiperone in the limbic forebrain, where D3 receptors are relatively abundant, but not in caudate-putamen, where D3 receptors are sparse. In nucleus accumbens antisense treatment also caused an increase in dopamine synthesis; in contrast, antisense administration did not counteract the effect of apomorphine on dopamine formation. No effect of antisense administration on dopamine synthesis was observed in caudate-putamen. The results support the usefulness of the antisense strategy for the study of D3 receptors and suggest that D3 receptors may influence dopamine synthesis.