Direct microinjection of cholinergic compounds into pontine reticular formation furnishes an excellent phenomenological model of the rapid eye movement phase of sleep (REM), but the mechanisms underlying this effect and whether they mimic the cellular events of natural REM remain unknown. Data presented here from intracellular recordings in vitro in the rat demonstrate that two-thirds of medial pontine reticular formation neurons respond to application of 0.5-1.0 microM carbachol with a depolarization characterized by a decreased conductance and a linear I/V curve. The resultant mimicry of REM cellular events by carbachol extends to membrane potential depolarization, increased cellular excitability, enhancement of PSPs from reticular stimulation, and the absence of a burst discharge pattern. The presence of these effects with tetrodotoxin and their blockade by atropine imply a direct, muscarinic cholinergic mediation. Other neurons tested responded with either a biphasic hyperpolarization-depolarization or a hyperpolarization. The hyperpolarization was associated with an increased conductance which exhibited pronounced inward rectification, an effect novel for cholinergic agonists in vertebrate CNS but described in heart cells.