Rapid index case treatment and amantadine prophylaxis were implemented in two nursing homes exposed to influenza A. Facility A had no isolation of cases, and 18 of 22 cases occurred after amantadine hydrochloride therapy was initiated. Three patients exhibited amantadine-resistant virus. Facility B had day 1 isolation of the index case. A facility-wide outbreak did not occur. The experience of these facilities suggests that concurrent amantadine treatment and prophylaxis without adequate case isolation may promote further influenza A infection in a nursing facility.