We have tested sera from 21 thymectomized patients with onset of MG after 40 years of age and without thymoma for antibodies against titin, using ELISA with the titin peptide MGT-30. Titin is a myofibrillar protein unique to striated muscle and important for the elastic recoil of muscle cells. Titin antibodies were detected in 9 of the 21 sera. MG symptoms as assessed by a 6 point disability score (0-5) were significantly more severe in the titin antibody positive patients both at peak of illness; 3.7 vs. 3.1 (p < 0.02) and at latest follow up; 2.1 vs. 0.8 (p < 0.01). All titin antibody positive patients were on immunosuppressive drug treatment at least follow-up, whereas only 3 of 12 patients without titin antibodies used immunosuppressive drugs. The presence of circulating titin antibodies in late-onset non-thymoma MG patients indicates a more severe disease.