The effects of biperiden (0, 100, and 320 μg/kg), a selective muscarinic M1/M4 receptor cholinergic antagonist, were studied alone and in combination with those of L-DOPA methyl ester (16.7 mg/kg), a selective dopamine D1 receptor agonist SKF-82958 (74.8 μg/kg), or a selective D2/D3 receptor agonist rotigotine (32 μg/kg) on circling behavior in MPTP induced hemiparkinsonian monkeys. The doses selected were given i.m. in approximately equieffective doses to produce contraversive circling. Biperiden alone with 5% dextrose vehicle produced a slight increase in contraversive circling in a dose related manner. When combined with L-DOPA methyl ester, it enhanced contraversive circling and decreased ipsiversive circling. When biperiden was combined with SKF-82958, contraversive circling also was enhanced and ipsiversive circling decreased. Exactly the opposite was observed with the combination of biperiden and rotigotine. The results indicate a dramatic difference in effects of a prototypic muscarinic M1/M4 receptor cholinergic antagonist in combination with prototypic full dopamine D1 or D2/D3 receptor agonists. Biperiden interactions with L-DOPA methyl ester were more predominantly Dl than D2/D3 receptor-like in this animal model of hemiparkinsonism.