To investigate the source of increased production causing elevation of serum immunoglobulin A (IgA) in ankylosing spondylitis (AS) we studied the production of IgA and IgA subclasses in cultures of bone marrow cells as well as the relative numbers of IgA and IgA subclass containing bone marrow cells obtained from 24 patients with AS and 22 healthy control individuals. In patients with AS serum levels of IgA, IgA, and IgA2 were significantly higher compared to controls. The IgA1 subclass in patient's serum contributed significantly less to the total IgA compared to controls. In bone marrow cultures of patients with AS and controls the production of IgA, IgA1 and IgA2 were in the same range as were the relative numbers of bone marrow cells containing IgA and IgA subclasses. However, the immunoglobulin synthesis by bone marrow cells of patients with AS showed a significant shift towards IgA1 compared to controls. Our findings indicate that the regulatory abnormalities of IgA production in AS involve both the IgA1 and IgA2 subclass and suggest that an abnormal mucosal immune response could be responsible for chronic overproduction of IgA and the elevation of serum IgA in patients with AS.