Annexin XI, a calcyclin-associated protein, has been shown to be identical to a 56,000 Da antigen recognized by antibodies found in sera from patients suffering from systemic autoimmune diseases. In this work hexahistidine-tagged recombinant annexin XI (His6- rAnn XI) was used as antigen in ELISA experiments for determination of autoantibodies to annexin XI in sera of patients with systemic rheumatic autoimmune diseases. Immunoblotting with HeLa cell extract and with His6-rAnn XI as antigen was used for confirmation of positive ELISA results. We found eleven anti-annexin XI positive sera (3.9%) out of 282 sera from patients with systemic rheumatic diseases. The highest number of annexin XI positive sera were found in primary antiphospholipid syndrome (3/17), and in subacute lupus erythematosus (1/6), while lower frequencies of positive sera were found in patients with systemic sclerosis (5/137), rheumatoid arthritis (1/21), and systemic lupus erythematosus (1/58). Sera from healthy donors and patients with chronic infections were negative, except for one Salmonella typhimurium antibody positive serum. Autoantibodies to annexin XI were found to relate to thrombosis, but not to other clinical or laboratory features. A relation between antibodies to annexins and thrombosis has so far only been known for annexin V.