A biophysical description of the axotomized rat sympathetic neuron is reported, obtained by the two-electrode voltage-clamp technique in mature, intact superior cervical ganglia in vitro. Multiple aspects of neuron functioning were tested. Synaptic conductance activated by the whole presynaptic input decreased to 29% of the control value (0.92 µS per neuron) one day after axotomy and to 18% after 3 days. Despite the decrease in amplitude of the macroscopic current, mEPSC mean conductance, acetylcholine (ACh) equilibrium potential and EPSC decay time constant were unaffected. Synaptic efficacy was tested during paired-pulse or maintained stimulation (5-15 Hz, 10 s duration). ACh release in axotomized neurons was preserved during the tetanus despite the reduction of the initial EPSC amplitude, suggesting that ACh secretion depended on the number of surviving synapses; each of them exhibited a dynamic behavior similar to that of normal synapses. Facilitation in quantal emission was noted in 2-day axotomized neurons during the first few seconds of maintained synaptic stimulation. Voltage-dependent potassium currents (the delayed I_KD and the transient I_A) exhibited an early drastic decrease in peak amplitude; these effects persisted 7 days after axotomy. Marked changes in I_A kinetics occurred following injury: the steady-state inactivation curve shifted by up to +17 mV toward positive potential and voltage sensitivity of inactivation removal became more steep. I_A impairment was reflected in reduced inward threshold charge for bursting and reduced spike repolarization rate. Synaptic and somatic data were pooled in a mathematical model to describe the progressive decrease in the safety factor, and the eventual failure of ganglionic transmission.