We studied 175 consecutive patients with ankylosing spondylitis (AS) to define the genetic characteristics of those patients who had associated acute anterior uveitis (AAU). The first 131 patients were tested for HLA antigens of the A and B loci, and the remaining 44 patients were typed only for HLA-B27. AAU was significantly more common in B27 positive patients, occurring in 40 of 144 B27 positive (27.7%) and in only 3 of 31 B27 negative patients (9.7%) (p less than 0.05). Among the B27 positive AS patients, AAU occurred in 24 of 68 patients (35%) who also possessed HLA-A2 and in only 5 of 35 patients (14%) who lacked A2 (p less than 0.025). An independent association of AAU with A2 could not be shown. In the absence of evidence of linkage disequilibrium between A2 and B27 in the general population, the data suggest that the presence of A2 in B27 positive AS patients enhances the risk of AAU above that associated with B27 alone, and that other MHC-linked genetic factors, in addition to B27, are associated with susceptibility to AAU in AS patients.