In order to get to clues about T-cell independent versus T-cell dependent immune mechanism in ALS, we measured IgG subclasses in 25 ALS-patients: 16 patients had deficiency of T-cell dependent expressed IgG1 or IgG3 or both with essentially normal levels of T-cell independent expressed IgG2 and IgG4. Ten of these patients had no prior treatment and five of these 10 had normal total IgG. Six patients had some immunosuppressive treatment before measurements of subclasses were done and all of them had deficiency of total IgG. Eight of 14 patients who underwent a d-xylose breath test, had evidence of small bowel overgrowth, which was confirmed by cultures of duodenal aspirate. IgG1 and IgG3 are T-cell dependent antibodies against protein antigens with close linkage on chromosome 14. The findings suggest a defect in the IgG subclass expression in ALS.