Among the rheumatic diseases, non so clearly illustrates the relations between host and environmental factors as the seronegative spondyloarthropathy group of disorders. The strongest association is with the histocompatibility antigen HLA-B27, which accounts for a striking susceptibility to these diseases and is present in over 90% of individuals with idiopathic ankylosing spondylitis. Next in importance appears to be a difference in sex penetrance with males predominating in all categories. The most dramatic sex relationship is with postvenereal Reiter's syndrome which has a male-to-female ratio of nearly 50:1. Another potent host factor is age, with increased predisposition to onset at puberty and young adulthood in HLA-B27-positive patients. Environmental or possibly infectious agent influence are most apparent in Reiter's syndrome, where the antecedent circumstances of venereal contact and bacillary dysentery are frequent precipitating events. Secondary forms of peripheral arthritis, radiographic sacroiliitis, and ankylosing spondylitis frequently occur in psoriasis and inflammatory bowel disease; in the case of peripheral arthritis, there is no or a significantly reduced association with HLA-B27 compared to AS or RS. Secondary factor seem to be contributing to spondyloarthropathy in these disorders. These iterrelations emphasize the powerful effects of host characteristics on the type of rheumatic disease syndrome acquired and provide superb opportunities for more precise understanding of disease pathogenesis and ultimate control through the integration of epidemiologic, clinical, and laboratory research.