Adult female Lewis rats were rendered immunologically tolerant to human gamma globulin, and were given a single intravenous injection of human myasthenic or normal control serum containing 7.5 to 12 mg of immunoglobulin G. The mean amplitude of miniature endplate potentials (MEPPs) in the forelimb flexor digitorum longus muscles from treated animals did not differ from control values during the first 24 hours after serum injection. Subsequently, MEPP amplitude was reduced in muscles from animals that had received myasthenic serum; maximum reduction was reached by 6 days after transfer. Mean MEPP amplitude at maximum reduction was 30 to 40% below the amplitude of controls and returned to control values 14 weeks after transfer. Similar reductions in endplate potential amplitudes were found in immunologically tolerant animals receiving myasthenic serum. No significant reduction of MEPP amplitude was seen in recipients that were not immunologically tolerant or that had received cobra venom factor to reduce complement activity. The delayed development of reduced MEPP amplitude indicated that the defect of neuromuscular transmission produced by myasthenic serum was not due entirely to a simple curare-like block of the acetylcholine receptor site by an IgG antibody.