An asynchronous firing or afterdischarge (AD) was recorded in vitro from the postganglionic internal carotid nerve of the rat superior cervical ganglion following repetitive stimulation of the preganglionic nerve when ganglion transmission was blocked by chlorisondamine, nicotine or hexamethonium, but was rarely observed in untreated ganglia. A stimulus frequency of at least 5 Hz was required to induce AD and as few as 100 pulses caused a significant response. The amplitude and duration of AD varied with the number of pulses. Low calcium solutions resulted in AD in the absence of ganglion blocking drugs, and high calcium solutions or low concentrations of atropine abolished the AD. Increasing magnesium concentration to 10 mM or the manganese concentration to 0.1 mM reduced or prevented AD following preganglionic nerve stimulation. The onset of AD was delayed in potassium-free solutions and at a lowered temperature. Dinitrophenol had a small depressant effect on AD but sodium azide reduced the amplitude significantly. Exposure of ganglia to bethanechol, 300 to 600 muM, resulted in asynchronous firing recorded from postganglionic nerves, and stimulation of the preganglionic nerve transiently depressed the drug-induced firing but enhanced the firing 30 to 60 seconds after the volley. Physostigmine did not alter the amplitude of bethanechol-induced firing after a volley. Prolonged high frequency (40 Hz) stimulation of the preganglionic nerve increased the AD following a 20 Hz test volley for up to 1 hour. It is concluded that increasing the release of acetylcholine or blockade of nicotinic receptors makes more acetylcholine available for interaction with muscarinic receptors, and that stimulation of the preganglionic nerve unmasks or sensitizes ganglionic muscarinic receptors. No clear evidence of a metabolic basis for the muscarinic response was obtained.