In the present study, the effects of bilateral injections of cholinergic agents into the hippocampal CA1 region on morphine-induced conditioned place preference (CPP) were investigated in male Wistar rats. Subcutaneous (s.c.) administration of different doses of morphine sulphate (0.5-6 mg/kg) produced a dose-dependent CPP. Using a 3-day schedule of conditioning, it was found that intra-CA1 administration of the anticholinesterase, physostigmine (2, 4 and 8 microg/rat) significantly potentiated the morphine (0.5 mg/kg)-induced CPP. Moreover, intra-CA1 administration of the muscarinic receptor antagonist, atropine (1, 4 and 7 microg/rat) inhibited the morphine (6 mg/kg)-induced CPP dose-dependently. On the other hand, atropine (7 microg/rat, intra-CA1) reversed the physostigmine-induced potentiation of the morphine response. Furthermore, intra-CA1 administration of nicotine (0.5, 0.75 and 1 microg/rat) with an ineffective dose of morphine (0.5 mg/kg) elicited a significant CPP. Bilateral injections of different doses of the nicotinic receptor antagonist, mecamylamine (2, 4 and 8 microg/rat) into the CA1 regions significantly inhibited the morphine (6 mg/kg)-induced CPP. Moreover mecamylamine (8 microg/rat, intra-CA1) decreased the effect of nicotine-induced potentiation of the morphine response. Intra-CA1 injections of physostigmine, atropine, nicotine or mecamylamine alone did not induce a significant place preference or place aversion. It may be concluded that the muscarinic and nicotinic receptors of the hippocampal CA1 regions play an important role in morphine reward.