INTRODUCTION: The association between infections and autoimmune diseases (AID) has been well described in the medical literature. Several infectious agents have been implicated as inducers of autoimmune responses, such as Parvovirus B19, Epstein-Barr virus, cytomegalovirus, and hepatitis viruses. PATIENTS AND METHODS: We examined 1,173 sera from patients with 14 different AID and 238 sera from geographically matched healthy controls, for evidence of prior infection with rubella. All samples were tested for the presence of serum antibodies against rubella using the Bio-Rad BioPlex 2200 system. RESULTS: As a group, patients with AID had a higher prevalence of IgM anti-rubella antibodies as compared to healthy controls (11.7% versus 5.4%; P = 0.001). The prevalence of IgM anti-rubella antibodies was significantly higher in 5/14 AID, namely in patients with giant cell arteritis (33.3%), primary biliary cirrhosis (24%), antiphospholipid syndrome (20.6%), polymyositis (16%), and inflammatory bowel disease (16%). A similar prevalence of IgM anti-rubella antibodies was detected among controls from different countries. A high prevalence of IgG anti-rubella antibodies was detected among patients with AID (89.9%) and controls. CONCLUSION: The increased prevalence of IgM anti-rubella antibodies in AID suggests a possible role for rubella in the etiopathogenesis of several AID.