Mantoux tests were performed on 200 children with culture-proven Mycobacterium tuberculosis infections. A group of 28 patients initially had negative reactions to 5 TU PPD-S. Of these, 17 had had extensive or overwhelming tuberculous disease at the time of admission, seven of whom reacted to 250 TU PPD; after a course of chemotherapy, all the survivors had positive reactions to 5 TU PPD-S. The 11 with less severe disease had negative reactions to 5 TU PPD-S and 250 TU PPD, as well as to PPD-A/B/G; in only two could a ready explanation be found for the negative reactor state. In general, a small number of children without life-threatening forms of tuberculosis may have persistently negative tuberculin reactions without any apparent cause. In such cases, other criteria for diagnosis must be relied on, such as lymphocyte transformation, culture, and biopsy.