Serum samples from 149 patients with RA and other rheumatological diseases, and 57 non-arthritic controls have been assayed for IgE antibodies to the cartilage collagen types II, IX and XI in their native and denatured state. Using an improved ELISA technique together with antigen-binding inhibition studies to confirm specificity, 10 of the 149 (7%) patients showed IgE antibodies to human collagen type II and bovine collagen types II, IX or XI. Some patients responded to only one collagen type whereas others had IgE positive responses to two or all three collagen species. Most of the IgE responses detected were directed towards the denatured collagens. Those sera showing an IgE response to bovine type II collagen produced a similar response to the human equivalent, including two patients with SLE. None of 57 control subjects demonstrated IgE specificity for any of the cartilage collagens. Patients with IgE specificity for the cartilage collagens did not demonstrate IgM or IgA specificity for these antigens, but two of these patients showed IgG responses to type II and XI collagens. Whereas eight patients were exclusively IgE-positive for the cartilage collagens, others expressed specificities for IgG, IgM or IgA. It therefore appears that the specific autoimmune profile for each patient is often different from others, both in terms of the class of immunoglobulin expressed and the collagen antigens recognised. At present no correlations were observed between the IgE-positive patients and their clinical assessment and/or prognosis.