The action of prednisolone at the neuromuscular junction was studied in mouse isolated phrenic nerve-diaphragm and rat external popliteal/sciatic nerve-tibialis anterior muscle preparations. Prednisolone (0.03 mM and 0.3 mM) did not alter the twitch-tension in phrenic nerve-diaphragm preparations after 120 min, but increased the frequency (170 +/- 4%) and amplitude (200 +/- 13%) of miniature end-plate potentials. Quantal content was not influenced by the glucocorticoid treatment. Prednisolone (400 mug/kg) did not change the twitch-tension in rat external popliteal/sciatic nerve-tibialls anterior muscle preparations. However, this steroid (0.3 mM) prevented the neuromuscular blockade by d-tubocurarine (1.45 muM) in mouse preparations by 70 +/- 10% (P < 0.05). A similar effect (82 +/- 6% protection, P < 0.05) occurred in rats treated with prednisolone (400 mug/kg) before d-tubocurarine (225 mug/kg). In phrenic nerve-diaphragm preparations, prednisolone (0.3 mM) increased (13 4%, p < 0.05) the twitch-tension in the presence of &beta;-bungarotoxin (1 &mu;M), and prevented the blockade produced by this toxin (0.15 &mu;M) in its third phase of action. This presynaptic facilitatory effect may contribute to the usefulness of prednisolone in myasthenia gravis. (C) 2002 Wiley Periodicals, Inc.2613743