The effect of D2 dopamine receptor activation on either the electrically, or N-methyl-D-aspartate induced release of radiolabeled acetylcholine (ACh) was investigated in different areas of the nucleus accumbens and the neostriatum of rats, by using a superfusion technique. Sequential slices of 100 microns were chopped along either a rostrocaudal, mediolateral or dorsoventral axis. In every slice the effect of a supramaximal concentration of the selective D2 receptor agonist quinpirole on the release of ACh was measured. In the entire neostriatum the release of ACh was reduced by approximately 70% in the presence of quinpirole. By contrast, in the nucleus accumbens, a gradual decrease in the inhibitory effect of quinpirole on the release of ACh was observed along both the rostral-to-caudal and the lateral-to-medial axes. Whereas in the rostrolateral part a 50% inhibition could be observed, in the caudomedial part no significant inhibition could be detected. Also the N-methyl-D-aspartate induced release of ACh was smaller in the caudomedial part as compared to the rostrolateral part of the nucleus accumbens. It is concluded that the nucleus accumbens is a very heterogeneous structure with respect to the regulation of the release of ACh by D2 dopamine and N-methyl-D-aspartate receptor activation.