The modulation of in vivo hippocampal ACh release by dopaminergic D1 and D2 receptors was examined in this study. Additionally, in an attempt to ascertain the location of these receptors in relation to hippocampal cholinergic terminals, fimbriaectomy and quantitative autoradiography were used. Following unilateral fimbriaectomy, whereby at least 50% of hippocampal cholineacetyltransferase (ChAT) activity was lost, a significant ipsilateral decrease in D1/3H SCH23390 binding was observed in the molecular layer of the dentate gyrus while hippocampal D2/3H raclopride binding was unaffected. The effects of prototypical D1 and D2 receptor agonists and antagonists on hippocampal ACh release were examined next using in vivo dialysis in freely moving rats. The D1 agonist SKF 38393 (10 microM to 100 microM) administered directly into the hippocampus via the dialysis probe stimulated ACh release in a concentration dependent manner. The effect of the agonist was blocked by the coadministration of the D1 receptor antagonist SCH 23390 (1 microM), which by itself failed to modulate ACh release. In contrast, neither the D2 agonist quinpirole (1–10 microM) nor the D2 antagonist sulpiride (1–10 microM) had any direct effect on hippocampal ACh release. Additionally, the infusion of these D1 and D2 drugs in the septal area failed to affect hippocampal ACh release. Taken together, these results suggest that a proportion of hippocampal D1 receptors are located on cholinergic nerve terminals and that dopamine, acting via D1 receptors, can locally stimulate hippocampal ACh release.