The major diseases associated with HLA-B27 (Reiter's disease, ankylosing spondylitis, acute anterior uveitis, and psoriatic arthritis) all occur much more commonly in men. Published evidence indicates that the antigen HLA-B27 is associated with high testosterone concentrations in men. Moreover, the antigen HLA-B44 exerts a protective effect on one of these diseases (psoriatic arthritis), and there are external grounds for supposing that HLA-B44 indexes an antiandrogenic process. These data are interpreted as support for the hypothesis (first adumbrated nearly 20 years ago) that HLA antigens index unusual hormone concentrations, which in turn are causally related to the diseases. An examination of published reports suggests that sibs of probands with ankylosing spondylitis (and perhaps Reiter's disease) contain an excess of men, and that sibs of probands with rheumatoid arthritis contain an excess of women. These data lend further support to the hypothesis.