A variety of recent evidence documents that otitis media is a frequent complication of upper respiratory tract viral infections. This relationship has been attributed to the interaction of a number of virus-provoked host responses, including eustachian tube dysfunction, changes in nasopharyngeal bacterial flora and suppressed immune function. The present study examined the effect of experimental influenza A virus infection on immune function as assessed by delayed skin test reactivity to candida, tetanus, and diphtheria/tetanus antigens in healthy adults with (n = 12) and without (n = 15) allergic rhinitis. All subjects became infected with the challenge virus as evidenced by viral shedding into nasal secretions and/or a four-fold rise in convalescent serum antibody titers compared to baseline. Intradermal skin tests were placed at baseline and 2, 4, 17, and 24 days after intranasal influenza A inoculation, the reactions were imaged and recorded 48 h after placement, and response areas were calculated by computerized digitization. The average combined areas for the three antigens (+/- S.T.D.) on each of the 5 study days were 1.4 +/- 1.4, 0.7 +/- 0.7, 0.6 +/- 0.6, 1.4 +/- 1.4, and 1.2 +/- 1.2 cm2, respectively. The responses to candida, but not tetanus and diphtheria/tetanus, returned to baseline levels by day 17. Repeated measures ANOVA documented significant effects of study day and antigen, but not allergy status. These results show that experimental influenza A infection suppressed delayed hypersensitivity skin tests in both allergic and non-allergic subjects, and suggest that alterations in immune function may contribute to otitis media.