1 Effects of 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on the neuro-effector junction of the guinea-pig vas deferens were investigated by microelectrode and double sucrose gap techniques. 2 4-AP (0.05 to 0.5 mM) or TEA (0.5 to 1 mM) did not alter the membrane potential, or the membrane input resistance of the smooth muscle cell. 3 The amplitude and frequency of the miniature junction potentials (m.e.j.ps) were not modified by treatment with 4-AP (0.05 to 0.5 mM) or TEA (1 mM). 4 4-AP (1 mM) increased the membrane input resistance, enhanced the spike amplitude of the smooth muscle cells and thereby augmented the amplitude of twitch contraction. 5 4-AP (.05 to 0.5 mM) or TEA (1 mM) markedly increased the amplitude of excitatory junction potentials (e.j.ps), but the facilitation phenomena produced by repetitive stimulation were not affected. 6 The duration of the extracellularly recorded action potential from the small nerve bundle was prolonged by 4-AP (0.5 mM). 7 The amplitude of the e.j.p. was dependent on the external concentration of calcium. A straight line was produced when the amplitude of the e.j.p. and [Ca]o was plotted on a double log scale. Application of 4-AP resulted in a parallel shift of this line to the left. 8 These results indicate that 4-AP (0.05 to 0.5 mM) and TEA (0.5 to 1.0 mM) prolonged the action potential generated from the sympathetic nerve terminal thus enhancing the amplitude of the e.j.p. due to an increase in the Ca-influx. However, in the concentrations used, these compounds did not modify the Ca-mobilization in the nerve terminal or the postsynaptic membrane during the resting state.