Brain microdialysis experiments were performed to assess the effects of calcium (1.2 mmol/l and 3.4 mmol/l) in the perfusion solution on a variety of pharmacological treatments known to affect the release of dopamine (DA) and/or acetylcholine (ACh). Intrastriatal infusion of the muscarinic receptor agonist oxotremorine (100 microM), the selective dopamine D-2 receptor agonist (-)-N-0437 (1 microM), and the indirect DA agonists (+)amphetamine (10 microM) and nomifensine (1 microM) via the dialysis probe did not affect the overflow of ACh when the perfusion fluid contained 3.4 mmol/l calcium. In contrast, these compounds produced pronounced decreases in the overflow of ACh at 1.2 mmol/l calcium. Intrastriatal infusion of the muscarinic receptor antagonist atropine (1 microM) increased the output of ACh both at 1.2 mmol/l and 3.4 mmol/l calcium. The selective DA D-2 receptor antagonist (-)-sulpiride (1 microM) did not affect the overflow of ACh at either calcium concentration. Infusion of oxotremorine and atropine had no effect on the overflow of DA at either 1.2 mmol/l at 3.4 mmol/l calcium. (-)-N-0437 decreased and (-)-sulpiride increased DA overflow, both effects being independent of the calcium concentration in the perfusion fluid. Nomifensine and (+)amphetamine caused relatively (but not absolutely) larger increases in the overflow of DA at 1.2 mmol/l calcium. These findings emphasize the critical importance of the calcium concentration of the perfusion fluid in determining the nature of pharmacological responses in microdialysis experiments, and demonstrate that locally applied dopaminergic drugs can modulate striatal cholinergic function.