To elucidate the mechanism of immune damage caused by titin and ryanodine receptor (RyR) autoantibodies in myasthenia gravis (MG), we studied the complement-activating capacity and the IgG subclass distribution of these autoantibodies in sera from 49 MG patients. Complement activation occurred in 38 out of 49 titin antibody positive sera, and in 14 out of 21 RyR antibody positive sera. The titin antibodies occurred only in the IgG 1 and IgG 4 subclasses, whereas the RyR antibodies occurred in all four IgG subclasses but with IgG 1 predominance. Complement-activating RyR antibodies occurred with higher frequency in sera of thymoma MG than of late-onset MG. RyR IgG 1 antibodies occurred more often in severe MG than in mild and moderate disease groups. Mean total IgG and IgG 1 titin and RyR antibody titers fell during long-time patient observation together with an improvement of the MG symptoms.