In late 1992, three cases of smear-positive tuberculosis were diagnosed among secondary school students in Lodi, Italy. The three attended different schools but travelled on the same bus. Schoolmates, other bus riders, family members, and friends underwent tine testing and X-rays. Of the 3188 students tested, 277 (8.7%) were reactors. Independent risk factors for tine reactivity among students included living in the same town (odds ratio [OR] = 4.8; 95% confidence intervals [CI] = 3.8-6.0); having classroom contact (OR = 4.4; 95% CI = 3.4-5.7); or riding the same bus (OR = 5.4; 95% CI = 4.3-6.7) as a smear-positive case. Twenty-four cases of pulmonary tuberculosis were identified. The index case was a student whose father had had cavitary tuberculosis. Despite being tine test positive in 1989, he was not given prophylaxis and was lost to follow-up. This large outbreak emphasizes the need for identification and prompt chemoprophylaxis of reactors, especially in vulnerable adolescent populations.