The mechanism of muscle weakness in myasthenia gravis and its possible relation to antibodies that are directed against the ryanodine receptor (RyR) were studied by the use of the spontaneous thymoma rat (Buffalo/Mna strain). The present study focused on the motor dysfunction as complicated by impaired subcellular machineries and noted particularly in patients with thymus abnormalities. Rats began to develop skeletal muscle weakness soon after birth and worsened progressively. Rats aged 3 months showed a benign thymoma characterized by proliferative lymphocytes; epithelial cells were stained with anti‐RyR peptide antibody. The rat serum contained anti‐RyR antibodies, but no anti‐acetylcholine receptor antibodies. The electrophysiological study in muscle showed a reduction of contractile force without abnormality in synaptic transmission and membrane properties, suggesting a defect in excitation–contraction coupling. Hypothetically, thymic epithelial cells and skeletal muscles share a common RyR antigen, so that anti‐RyR antibodies that target the thymic tissue may react with a homologous target in the muscle. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1655–1660, 1998