Non-nicotinic slow synaptic currents were recorded from voltage-clamped neurones in isolated rat superior cervical ganglia bathed in a solution containing d-tubocurarine and (usually) 1 microM-neostigmine. Three components of slow synaptic current could be detected following repetitive preganglionic stimulation: a net inward current resulting from inhibition of the voltage-dependent outward K+ current IM; a net outward current associated with a fall in membrane conductance when IM was deactivated by membrane hyperpolarization or inhibited with external Ba2+ or internal Cs+; and an occasional late inward current associated with an increased membrane conductance. As a result, synaptic current amplitudes showed complex changes with changes in membrane potential. Both the inward current associated with IM inhibition and the outward current were enhanced by neostigmine and blocked by atropine or pirenzepine, and therefore resulted from activation of muscarinic receptors. In unclamped neurones, equivalent stimulation produced a membrane depolarization and induced or facilitated repetitive spike discharges. It is concluded that the principal synaptic response to muscarinic receptor activation is IM inhibition, leading to a net inward current and increased excitability, but that this response may be modified under certain circumstances by other synaptic currents.