Increased vaccine doses and mid-season boosting may increase the proportion of residents with protective immunity from influenza in long-term care facilities. In a multi-center study (1997-1998), 815 residents from 14 long-term care facilities were assigned at random to receive 15 or 30 microg of inactivated influenza vaccine, followed by a 15 microg booster vaccine or a placebo vaccine at Day 84. Seroresponses were re-analyzed by hemagglutination-inhibition (> or =4-fold titer increases, protective titer > or =40, geometric mean titers. Forty percent of the participants had pre-vaccination titers > or =40. At Day 25 after vaccination, this increased to 66.3% after a 15 microg dose versus 73.3% after a dose of 30 microg (P = 0.049). Participants receiving a 30 microg dose followed by a 15 microg booster showed more > or =4-fold titer increases at Day 109 (43.6% vs. 35.4%, P = 0.003) and protective titers > or =40 (74.2% vs. 64.6%, P = 0.041), compared to those receiving only a 15 microg dose. Differences were most apparent in participants with low pre-vaccination titers. Booster vaccination after an initial 15 microg dose of the vaccine did not increase the protective rate (61.9% vs. 63.9% after placebo). The number of participants needed to vaccinate to protect one additional resident by a dose of 15 microg was 4, by a dose of 30 microg 3, and 15 when using a 30 microg dose instead of 15 microg. Doubling the dose of influenza vaccine increased protection-related responses among residents of long-term care facilities, especially in those with low pre-vaccination titers.