OBJECTIVE: To evaluate the antibody response to influenza vaccines in nursing home residents and healthcare workers (HCWs) and its relation to residents´ functional and chronic disease status during four successive seasons. DESIGN: Before-after study. SETTING: Nine nursing homes during the 1998-1999 season and two during the 1999-2000, 2000-2001, and 2001-2002 seasons. PARTICIPANTS: Two hundred fifty-nine residents and 79 HCWs during the 1998-1999 season; 180 and 71, respectively, during the 1999-2000 season; 162 and 71, respectively, during the 2000-2001 season; and 153 and 79, respectively, during the 2001-2002 season. RESULTS: Multivariate analysis indicated that the mean fold increase in the geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibodies and the response rate (the proportion of vaccinees resulting in a significant, at least fourfold increase in antibody titer) were good and no significant differences occurred for almost all strains in both residents and HCWs. The GMTs of HI antibodies and the protection rate (the proportion of participants with HI antibody titers > or = 40) were increased in both residents and HCWs, but were significantly lower for almost all strains in residents than in HCWs. Furthermore, multivariate analysis indicated that subdivision of residents into three groups by level of daily activities and into four groups according to underlying diseases revealed only minor differences in immune responses. CONCLUSIONS: Antibody responses to the influenza vaccine were lower in residents than in HCWs. However, residents showed similar antibody responses regardless of their level of daily activity or underlying diseases.