A ferret model was used to study bacterial adherence in animals with influenza. Ferrets were inoculated intranasally with influenza A3/Hong Kong/1/68 virus. Antiviral serum antibodies were apparent by Day 5. On Days 3, 5, 7, 9, and 11, three virus-inoculated and two uninoculated controls were anesthetized, exsanguinated, and decapitated, and the lower jaw was removed. Each animal was inoculated intranasally with a 1-ml suspension containing 20 mg (dry wt) of either 3H-labeled Staphylococcus aureus or 3H-labeled group B Streptococcus type Ia and incubated for 45 min at ambient temperature. In animals challenged with staphylococci, 80% of the original inoculum remained free in suspension; of the remaining 20%, the distribution in the upper respiratory tracts of virus-infected and control animals was significantly different. Of the staphylococci remaining in the nasopharynx of control animals, 74% was present in mucinous plugs, 11% was bound to host cells present in washes of the nasal cavity, and 15% was released by protease treatment of the nasopharynx. Of the staphylococci remaining in the upper respiratory tract of virus-infected ferrets, 36% was recovered in plugs, 24% was bound to cells in nasal washes, and 40% was released by enzyme treatment. Overall, adherence-positive staphylococci represented 64% of recoverable bacteria in virus-infected ferrets versus 26% in controls. Adherence was increased twofold (Days 5 and 7) to threefold (Days 3, 9, and 11) in virus-infected ferrets compared to uninfected controls. In contrast, only 7% of the original streptococcal inoculum was recovered from virus-infected and uninfected control animals and virus infection did not enhance streptococcal adherence except for an approximately threefold increase that was seen on Day 11.