To evaluate the occurrence and outcome of acute otitis media (AOM) in human immunodeficiency virus (HIV)-infected children, a prospective comparative cohort study was performed. Twenty-seven HIV-infected children were individually matched with paired control subjects and followed up for 543 months (mean 19.4 +/- 11). Data collected were evaluated considering HIV-infected children both as a whole and as P1 and P2 patients according to Centers for Disease Control classification. During the observation period, 46 episodes of AOM were diagnosed in 15 HIV patients and 22 in 16 control children: 11 P1 had 27 AOM episodes vs 17 in 13 control children; 6 P2 had 19 AOM episodes vs 5 in 4 control children. Human immunodeficiency virus infection does not seem to modify the occurrence of AOM. Recurrent AOM (3 or more episodes in 6 months) was, however, significantly more common in P2 children. Amoxicillin, to which the bacteria isolated in P2 children were sensitive in vitro, cured 33 of 46 episodes in HIV-infected children compared with 20 of 22 in control children. Cure rate was similar in P1 children compared with control children but was significantly lower in P2 versus control children (47.3% vs 100%). Reasons for higher occurrence of failures in P2 children remain to be investigated.