1. Experiments using intracellular recording, stimulation, and microionophoretic techniques were performed on extensor digitorum longus nerve-muscle preparations excised from mice having hereditary 'motor end-plate disease'. Control experiments were performed on normal innervated and chronically denervated nerve-muscle preparations. 2. Two physiologically distinct groups of muscle fibres were found in the diseased muscles. Group I is similar to normal innervated muscle with respect to resting potentials, cable properties, neuromuscular transmission, miniature end-plate potentials, and extrajunctional acetylcholine sensitivity. Group II is similar to denervated muscle in the above respects except that (i) neuromuscular transmission, though abnormal, was present, and (ii) miniature end-plate potentials (m.e.p.p.s), often having large amplitudes, were found in these muscle fibres. 3. Large m.e.p.p.s appear to be due to an increase in muscle fibre input resistance and to the quantal release of abnormally large amounts of acetylcholine from motor nerve terminals. 4. Nerve stimulation of group II muscle fibres evoked action potentials with a delayed repolarization phase, suggesting that a prolonged acetylcholine-induced conductance change occurs at motor end-plates. 5. Neuromuscular physiology in motor end-plate disease is similar to that reported for frog nerve-muscle preparations which have been incubated in high Ca2+ Ringer.