Lntracellular microelectrode recording of miniature end-plate potentials (MEPPs) was used to investigate the effect of prednisolone on neuromuscular transmission in the rat phrenic nerve-diaphragm preparation. Prednisolone facilitated spontaneous release of acetylcholine as manifested by a twofold to threefold increase in MEPP frequency, and it decreased MEPP amplitude by about 50 percent. Both effects were reversible after prednisolone washout. These data suggest that the early alterations and short-term fluctuations in myasthenic weakness seen in patients being treated with corticosteroids may 15e attributed at least in part to a direct effect on neuromuscular transmission.