Endplate potentials (EPP's) and miniature endplate potentials (MEPP's) were recorded from neuromuscular junctions of the mouse phrenic nerve-diaphragm preparation, blocked by high Mg++ (12 X 10(-3) mol/l)-Ringer. Superfusion of the preparations with Mg++-Ringer solutions containing thallium acetate (5 X 10(-4) mol/l Tlac) decreased phasic transmitter release as judged by EPP amplitudes as well as average quantal content, until total synaptic blockade (within about 300 min) occurred. Simultaneously MEPP amplitudes remained unchanged, whereas the frequency of MEPP's increased. When EPP amplitudes and/or quantal content were reduced by 50% (usually within about 180 min), superfusion with Mg++-Ringer solution without Tlac did not restore phasic transmitter release. However, the increase in spontaneous transmitter release was reversible, as MEPP frequencies returned to normal values. 4-Aminopyridine (5 X 10(-4) mol/l 4-AP) as added to the bath solution in the state of 50%-reduced phasic release temporarily restored EPP amplitudes and average quantal content, whereas MEPP amplitudes remained unchanged. It is concluded that thallium irreversibly blocks phasic transmitter release, whereas spontaneous transmitter release is reversibly enhanced.