A prospective study, with an attempted 24-month-post-treatment follow-up, of children with tuberculosis (TB) treated with short course chemotherapy (SCC) for 6 months was carried out because published experience of SCC in childhood TB was limited. All children in Port Moresby diagnosed as having TB between November, 1984, and November, 1986, entered the trial. Of the 639 children 165 (26%) were younger than 2 years old. Of these, 227 (35%) had extrapulmonary TB (peripheral lymph node, 110; central nervous system, 43; abdominal, 27; miliary, 16; bone and joint, 11; pleural, 11; polyserositis, 9). Clinical response to SCC was rapid. Adverse drug reactions occurred in 15 (2%), mainly to streptomycin. Twelve (2%) died, 38 (6%) transferred out and 145 (28% of the 518 who did not die, transfer or live too far from a treatment centre) defaulted. Three hundred seventy-three (58%) completed a 2-month course of daily rifampin, isoniazid, pyrazinamide and streptomycin followed by a 4-month course of twice weekly rifampin and isoniazid. A further 71 (11%) had their treatment modified because of their distance from a treatment center. Only 70 (19%) of the 373 children available for post-treatment follow-up attended the every-3-month follow-up visits for 24 months, although 223 (60%) attended one or more of the follow-up visits. Seven of the 373 children relapsed, mostly within 3 months. Five of these children had been irregular with their treatment. SCC for childhood TB is safe and effective for pulmonary and extrapulmonary disease.