The effects of cholinergic drugs on the in vivo release of dopamine (DA) and its metabolites were studied in the striatum of freely moving rats. The endogenous compounds were sampled by microdialysis and analysed by on-line HPLC. High doses of oxotremorine (5 mumol/kg), physostigmine (3.6 mumol/kg), nicotine (3 mumol/kg) and atropine (10 mumol/kg) were injected i.p. Oxotremorine, physostigmine and atropine failed to modify the release of DA, while nicotine induced a slight (30%) but significant increase in the release of the transmitter. In contrast, oxotremorine and physostigmine did produce a significant rise of the dialysate contents of the DA metabolites. Thus, these data demonstrate clearly that changes in DA metabolism do not necessarily reflect changes in the release of DA. The most interesting findings of the present study is the fact that muscarinic receptor stimulation or blockade does not modify the release of DA from the rat striatum, while nicotine receptor stimulation may exert some stimulatory effect on the release of DA. This conclusion does not support the concept that the mode of action of anticholinergic drugs used in the treatment of parkinsonism, can be ascribed to a modulation of striatal dopaminergic activity.