The prevalence of serum leukocyte-reactive antinuclear antibody (LR-ANA) was determined in 31 patients with ankylosing spondylitis (AS), their age-and gender-matched normal controls, and two tribes of 340 West Coast Canadian Indians (Bella Coolas and Haidas). At a serum dilution of 1 : 10, the prevalence of LR-ANA in AS and controls was 45% and 7%, respectively. At 1 : 20 dilution, the prevalence was 23% in AS, 0% in controls, 29% in Bella Coolas and 27% in Haidas. No concordance was found among LR-ANA, HLA-B27 and CREG-B7, and nine HLA-A and seven HLA-B antigens in the Indian tribes. These studies confirm an increased prevalence of LR-ANA in AS and AS kindreds, but the latter association appears to be independent of HLA antigens.