The effect of DHEA administration on the age-associated decline in immunity against influenza vaccine was studied. Increased humoral response was observed in 16- and 24-month-old mice immunized by live A/PR/8/34 (H1N1) influenza virus following DHEA treatment (a single injection adjacent to immunization). Furthermore, DHEA-treated mice demonstrated increased resistance to postvaccination intranasal challenge with live influenza virus. Thus, DHEA treatment overcomes the age-related defect in the immunity of old mice against influenza.