Presynaptic D2-like receptors appear to mediate the stimulus properties of a low dose (0.05 mg/kg) of the D2-like agonist quinpirole (QUIN), because treatments decreasing dopamine (DA) release or blocking postsynaptic DA receptor activation produce QUIN-appropriate responding in a drug discrimination context, whereas treatments activating postsynaptic DA receptors evoke saline responding (28). This study examined the hypothesis that training to a presumably postsynaptic dose of QUIN (0.20 mg/kg) would produce the opposite pattern of effects. Using drug discrimination procedures, substitution for 0.05 mg/kg (28), but not 0.20 mg/kg QUIN, was produced by the D1 antagonist SCH23390, the catecholamine depleter alpha-methyl-paratyrosine and low doses of apomorphine (up to 0.25 mg/kg). The D2 agonist NPA substituted fully for 0.05 but only partially for 0.20 mg/kg QUIN. Cocaine and d-amphetamine (alone or with SCH 23390) substituted only minimally for either QUIN training dose. The putative D3 agonist 7-OH-DPAT engendered primarily saline responding when substituted for 0.20 QUIN. The 0.20 QUIN stimulus was antagonized by the D2 blocker haloperidol and partially blocked by the D1 antagonist SCH 23390. These data show a clear difference in the mediation of the stimulus properties of a low (0.05 mg/kg) vs. a high (0.20 mg/kg) dose of QUIN and are suggestive of a preferential postsynaptic D2 mediation of the 0.20 mg/kg QUIN dose.