Amantadine, in a dose of 100 mg/day, is recommended for influenza prevention in older nursing home residents. We studied an influenza prevention protocol in a 98-bed community nursing home (96% female; mean age = 87.4 years). Fifty-five residents received amantadine when influenza A was confirmed. Although no further influenza cases were diagnosed, 22% experienced adverse events. Dose in mg/kg/day was significantly higher in the group experiencing adverse events (2.24 +/- 0.98 vs 1.76 +/- 0.35; P less than .01). Amantadine concentrations in 32 residents ranged from 128-5,810 ng/mL. Six residents had amantadine concentrations greater than 1,000 ng/mL. Seventy-eight percent would have qualified for further dose reduction on the basis of estimated creatinine clearance. The results suggest that adverse events may be an important problem with the 100 mg/day dose, and this dose may be excessive for influenza prophylaxis in many nursing home residents.