Ankylosing spondylitis (AS) is strongly associated with the major histocompatibility complex (MHC) class I antigen HLA-B27. This may have influence on the physiologic immune response. Whether it leads to an increased prevalence of infections and/or allergy in AS patients is unclear. This study aims to determine the prevalence of infections and allergic symptoms in patients with AS and to detect a possible association with clinical symptoms. Data on 1,080 AS patients and on 102 disc prolapse patients were collected by questionnaire. The proportion of patients with a symptomatic infection in the last year was 65.5% in AS patients in comparison with 25.5% in disc prolapse patients (p=0.0001). AS patients reported more gastrointestinal (GI) [odds ratio (OR) 5.07, 95% confidence interval (CI) 2.20-11.71], urinary tract (OR 2.81, 95%CI 1.41-5.72), and respiratory (OR 5.83, 95%CI 3.38-10.08) infections than did disc prolapse patients. Multiple infections were more common in AS patients across all infection types. Allergic symptoms were reported by AS patients more frequently than by disc prolapse patients (OR 5.13, 95%CI 3.49-8.80). Patients reporting concurrent inflammatory bowel disease were more likely to report GI (OR 3.0, 95%CI 1.9-4.8) and urinary tract (OR 1.7, 95%CI 1-2.8) infection than primary AS patients. In AS patients, infection was independently associated with female gender (OR 1.96, 95%CI 1.47-2.56), a history of significant peripheral joint inflammation (OR 1.55, 95%CI 1.18-2.05), and increasing pain duration (p=0.05). A high prevalence of common infections and allergic symptoms is seen in patients with AS, most of which are HLA-B27-positive. This may have implications both for underlying mechanisms of disease and for therapeutic options.