The toxicity of myasthenic sera to rat myotubes in monolayer culture was examined by measuring the release of [Me-3H]carnitine from pre-loaded cells. In the presence of guinea pig complement, heat-inactivated serum samples from 9 out of 13 myasthenic patients showed clear myotoxicity, in contrast to 0 out of 11 normal controls and 0 out of 6 polymyositis patients. Neither heat-inactivated sera alone nor guinea pig complement sera alone showed myotoxicity. Removal of anti-acetylcholine receptor (anti-AChR) antibodies from a myasthenic serum sample by affinity absorption led to loss of myotoxicity. Myotoxicity of myasthenic sera could, in most cases, be confirmed by light microscopy. These results support the idea that complement-mediated cell damage, initiated by anti-AChR antibodies, contributes to post-synaptic membrane degeneration in myasthenia gravis.