1. Muscarinic modulation of nicotinic transmission was studied in bullfrog sympathetic ganglia by recording synaptic currents from B and C neurones. 2. Bath-applied muscarine reduced the amplitude of EPSCs recorded at < 0.2 Hz from B neurones by up to 57%. The action was reversible, showed no apparent desensitization, and had an EC50 of 102 nM. Muscarine had no effect on EPSCs in C neurones. 3. Currents evoked by ionophoretic application of ACh to B neurones were unchanged by muscarine. Muscarine increased the coefficient of variation (c.v.) of EPSC amplitude. The effect upon the ratio of c.v.2control to c.v.2muscarine was proportional to the change in mean EPSC amplitude. 4. Activation of muscarinic receptors by ACh from nerve terminals was observed by comparing trains of EPSCs in normal Ringer solution and atropine. Inhibition of EPSC amplitude by 15-40% was seen as frequency was increased from 1 to 5 Hz. The minimal latency for onset of inhibition was approximately 2 s. Stimulation at 20 Hz did not produce inhibition. 5. The results indicate that presynaptic muscarinic receptors are selectively expressed by a functional subclass of preganglionic sympathetic nerve terminals. Physiological activation of the receptors occurs during repetitive activity. The extent of autoreceptor-mediated inhibition varies as a biphasic function of stimulus frequency.