1. During presynaptic inhibition, an increased conductance in the membrane of the presynaptic bouton is presumed to reduce the action potential, thereby reducing transmitter release. The object of the simulation has been to determine the magnitude of a chloride conductance required to reduce transmitter release, for various diameters of synaptic boutons, connected to axons with diameters in the range 0.1-1.0 microns. 2. A propagating action potential was simulated in axons connected to either side of a hemispherical bouton. The axons could be myelinated or unmyelinated, while the bouton membrane could be passive, a node of the myelinated nerve, or have the same active properties as the attached unmyelinated nerve. Membrane properties of the axons were derived from mammalian data and scaled to 37 degrees C. 3. A steady-state chloride conductance was included in the bouton membrane, with ECl = -40 mV. The amplitude of the action potential in the bouton was calculated for different diameters of axon and bouton and for different magnitudes of chloride conductance. 4. Using published data on the relationship between the amplitude of a presynaptic action potential and the resulting postsynaptic potential, the relationship between the chloride conductance and the postsynaptic response was calculated for different geometries. Transmitter release was reduced when an action potential was 90 mV or smaller, with no transmission for action potentials smaller than 50 mV. 5. Conductance increases in the range 3 to 10 nS were required to reduce the action potential to 90 mV, depending on the diameter of the axon (0.5-1.0 microns), diameter of the bouton (3-6 microns), whether the bouton had passive or active membrane, and whether the axon was myelinated or unmyelinated. A 3 microns passive bouton connected to a 0.5 micron myelinated axon was most sensitive to the effects of a chloride conductance, while a 6 microns active bouton connected to a 1 micron myelinated nerve was least sensitive to the effects of a chloride conductance. 6. The reduction in the action potential was compared when ECl = -40 mV and when ECl = E(rest) = -80 mV. Inactivation of the sodium conductance by terminal depolarization was the dominant influence on the amplitude of the action potential. 7. Conductances that were sufficient to completely block synaptic transmission at a bouton were insufficient to prevent the spread of the action potential away from that bouton.(ABSTRACT TRUNCATED AT 400 WORDS)