Background and Methods: Patients with pulmonary tuberculosis who are sputum smear-negative and particularly young children without cavitating lesions have previously not been considered to be infectious. Following the diagnosis of pulmonary tuberculosis in a 9-year old boy (the index case) with a right upper lobe consolidation and Mycobacterium tuberculosis grown from a smear-negative sputum, we detected a high rate of infection in his family and class contacts. This led to the screening of all pupils (n = 200) and staff (n = 108) of a UK junior school for M. tuberculosis infection. Results: Altogether, 85 (42%) pupils of the junior school had a reactive gamma interferon release assay indicating infection with M. tuberculosis. X-ray screening revealed 18 children with pulmonary changes consistent with tuberculosis. One child had acid-fast bacilli on gastric lavage but there was no increased rate of infection among his family or class contacts. The infection rate in the class of the index case was significantly higher (79%) than the infection rate among the other pupils at the school (35%) (p <0.01). None of the adult contacts screened had pulmonary tuberculosis. Genetic finger printing revealed that the strain of M. tuberculosis of the two pupils was identical and matched a strain of a family contact of the index case (and the most likely source for this school outbreak) encountered six years previously. Conclusions: Smear-negative sputum and lack of cavitating disease on a chest x-ray do not exclude significant risk of transmission of infection from a patient with pulmonary tuberculosis.