The serum levels of IgM-Rheumatoid Factor and of anti-F(ab')2 autoantibodies were investigated in patients with inflammatory Bowel Disease (IBD) by sensitive radioimmunoassays. Serum levels of the 2 autoantibodies were significantly increased in active IBD. In patients with Crohn's Disease raised titers of the 2 antibodies appeared to be also related to colonic involvement. There was, in Crohn's Disease, a significant association between concordantly positive results with the 2 assays and the occurrence of systemic complications. Immunocomplexes detected by the C1q-SP method were higher in sera of Crohn's Disease patients with raised IgM-RF than in the others. Data from the present investigation indicate that in active IBD and particularly in Crohn's Disease autoantibodies directed against different parts of the immunoglobulin molecule may be produced. These findings add support to the concept that an in vivo polyclonal B-cell activation may occur in these patients.