The present study was performed on 61 HLA-B27 positive first-degree relatives and 40 HLA-B27 negative relatives of 20 HLA-B27 positive probands with ankylosing spondylitis (AS). Of 24 HLA-B27 positive relatives 45 years or older, 21% had AS and 38% sacroiliitis. The HLA-B27 negative relatives did not have features of either disease. In the population study of 2,957 individuals 45 years or older, we found 5 cases of HLA-B27 positive sacroiliitis (according to the New York criteria) and 3 of these fulfilled the New York criteria for diagnosis of AS. In 2 of these 3 individuals, the diagnosis was made on clinical grounds. The pheno-type frequency of HLA-B27 in this population is 7.8%, or about 230 HLA-B27 positive individuals in this population sample. Since AS was found in only 3 individuals, 1.3% of the HLA-B27 positive individuals in the population at large have AS; therefore, our data show that among individuals 45 years or older, 21% of HLA-B27 positive relatives of HLA-B27 positive AS patients have AS as compared with 1.3% of the HLA-B27 positive individuals in the population at large. Thus, the risk for AS is 16 times greater in the HLA-B27 positive relatives compared with HLA-B27 positive individuals in the population at large. The discriminatory value of the New York criterion of history of pain or the presence of pain at the dorsolumbar junction or in the lumbar spine was analyzed in the population and family studies and was found to be too nonspecific.