This study was undertaken to clarify the role of complement in acetylcholine receptor loss and degeneration of the postsynaptic membrane in myasthenia gravis (MG). We examined the end-plate morphology in rats with passively transferred immunoglobulin G (IgG) from myasthenic patients and the effect of complement by treatment of the rats with cobra venom factor. We injected peroxidase-labeled alpha-BuTx (P-BuTx) into the extensor digitorum longus (EDL) muscle to label the motor end-plates. Three hours later, 100 mg of IgG from MG patients or healthy controls was injected into the tail vein. The EDL was removed 48 hours after the injection of IgG. The presence of macrophages and degeneration of the postsynaptic membrane were seen in 4 of 6 IgG samples from MG patients and a decrease in AChRs in the other 2 samples. These changes were reversed completely by treatment with cobra venom factor in all but one case in which the end-plates were severely degenerated. Injection of MG IgG only never induced end-plate morphology changes. The results suggest that complement has a critical role in degeneration of the postsynaptic membrane and AChR loss at the motor end-plates in the passively transferred model and probably in human MG.