Abstract: Ankylosing spondylitis (AS) is a chronic inflammatory condition associated with HLA B27. But the association is not absolute. Hence association with other HLA class I antigens and class II alleles was studied in a southern Indian population. Sixty-five patients with primary AS were typed serologically for HLA class I antigens. Age- and sex-matched disease controls (37 with enterogenic reactive arthritis [ReA] and 25 with undifferentiated spondyloarthropathy [UnSpA]) and 124 healthy controls were studied. PCR-based DNA-SSO typing for DQA1 and DQB1 was performed on 20 patients with AS and 38 healthy controls. Twenty-three patients with AS and 39 controls were typed for DRB1 alleles. HLA B27 was positive in 76.9 % of the cases of AS (RR 811), 59.5% of those with ReA (RR 9.3), and 40% of the patients with UnSpA (RR 9.3), while none of the controls were B27 positive. The P value for positive association was highly significant for B27 in all the three groups. B27 positivity was associated with earlier age of onset of disease in all the diseases compared to the B27-negative group. HLA Cw2 was positively associated with AS (P highly significant; OR 52) and ReA (P= 0.0003; OR 14.2). HLA A1 and CW6 were significantly negatively associated only with AS (P= 0.0001 and 0.00004 and OR 0.25 and 0.02, respectively). None of the HLA class II alleles were significantly associated with AS. The apparent association with DRB1*11 (P= 0.03) was lost after Yates correction.