Clinical data suggest the involvement of hereditary factors in children susceptible to recurrent acute otitis media. That relationships of varying degree exist between the frequencies of certain HLA antigens and various disease entities is well established. In the present study, we investigated the frequencies of a number of HLA antigens in 45 patients with clinical recurrent acute otitis media and compared these frequencies with those in a control group from the same district. The HLA-A2 antigen occurred in 80% (36/45) of the group with recurrent acute otitis media, as compared with 56% of controls. Of a subgroup of 11 children with recurrent acute otitis media who were prospectively followed up, 10 (91%) were HLA-A2 positive. The HLA-A3 antigen occurred in only 11% (5/45) of the group with recurrent acute otitis media as a whole (n = 45) in comparison with 28% of controls. Among 22 prospectively followed up children without any episode of acute otitis media during the first 3 years of life, the frequency of HLA-A2 was 45% (10/22) and that of HLA-A3, 32% (7/22). The results indicate the existence of a relationship between recurrent acute otitis media and the HLA-A locus, suggesting the involvement of genetic factors in the disease.