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Background. Two doses of trivalent inactivated influenza vaccine (TIV) are recommended for children ! 9 years old receiving vaccine for the first time, but compliance is suboptimal. This study assessed the need for a second dose of TIV in this age group. Methods. In this prospective, open-label study, 232 influenza vaccine-naive 5-8-year-olds enrolled in a health maintenance organization received 2 doses of TIV in fall 2004. Serum for antibody titer measurement was obtained at 3 time points (n = 222). Parents completed diaries for 5 days. Results. Both doses of vaccine were well tolerated. The strongest predictor of a protective antibody response (>= 1:40) after 1 dose of TIV was baseline seropositive status. In multivariate analysis adjusting for age, sex, and baseline serostatus, the proportion of children with protective antibody responses was significantly higher after 2 doses than after 1 dose of TIV for each antigen (P <.001, for A/H1N1; P = .01 for A/H3N2; P <.001, for B). Age and sex were not independently predictive of a protective antibody response. Over one-third of children had antibody responses ! 1: 40 for the type B vaccine component, even after 2 doses. Conclusions. The present study supports the need for 2 doses of TIV in 5-8-year-olds receiving TIV for the first time. Efforts to increase compliance with the 2-dose recommendation are warranted