BACKGROUND: The tuberculin skin test (TST) is often used to screen for latent tuberculosis infection (LTBI) in school children, many of whom were bacille Calmette-Guérin (BCG)-vaccinated in infancy. The reliability of the TST in such children is unknown. METHODS: TSTs performed in low-risk BCG-vaccinated and -nonvaccinated grade 1 and grade 6 First Nations (North American Indian) school children in the province of Alberta, Canada, were evaluated retrospectively. To further assess the specificity of the TST, BCG-vaccinated children with a positive TST (=10 mm of induration) and no treatment of LTBI were administered a QuantiFERON-TB Gold In-Tube test (QFT-GIT, Cellestis International). RESULTS: A total of 3996 children, 2063 (51.6%) BCG-vaccinated and 1933 (48.4%) BCG-nonvaccinated, were screened for LTBI. Vaccinated children were more likely than nonvaccinated children to be TST positive (5.7% vs. 0.2%, P