Proposed measures to contain pandemic influenza include school closure, although the effectiveness of this has not been investigated. We examined the effect of a nationwide elementary school strike in Israel in 2000 on the incidence of influenza-like illness. In this historical observational study of 1.7 million members of a preferred provider organization, we analysed diagnoses from primary-care visits during the winter months in 1998-2002. We calculated the weekly ratio of influenza-like diagnoses to non-respiratory diagnoses, and fitted regression models for school-aged children, children's household members, and all other individuals aged >12 years. For each population the steepest drop in the ratio of influenza-like diagnoses to non-respiratory diagnoses occurred in the strike year 2 weeks after the start of the strike. The changes in the weekly ratio of influenza-like diagnoses to non-respiratory diagnoses were statistically significant (P=0.0074) for school children for the strike year compared to other years. A smaller decrease was also seen for the adults with no school-aged children in 1999 (P=0.037). The Chanukah holiday had a negative impact on the ratio for school-aged children in 1998, 1999 and 2001 (P=0.008, 0.006 and 0.045, respectively) and was statistically significant for both adult groups in 1999 and for adults with no school-aged children in 2001. School closure should be considered part of the containment strategy in an influenza pandemic.