Prednisolone, in concentrations of 0.004--0.032 mmol/l, increased the amplitude of the miniature end-plate potentials (MEPPs). A maximum increase to 134% of the control values was seen at 0.016 mmol/l. At higher prednisolone concentrations the MEPP amplitude gradually decreased to reach 77% of the control value at 0.62 mmol/l. The MEPP frequency was increased to twice the control value at 0.62 mmol/l. The quantal content of the end-plate potential (EPP), however, was not influenced by prednisolone. The response to iontophoretically applied acetylcholine was diminished, especially at 0.62 mmol/l prednisolone. Prednisolone, therefore, caused presynaptic effects as was shown by an increase in unitary MEPP amplitude and by a considerable number of giant MEPPs, which at increasing prednisolone concentrations was antagonized increasingly by a postsynaptic depressant effect. These results also provide an explanation for the adverse effects of prednisolone on the end-plate potential and on neuromuscular transmission.