Fifty-two children with tuberculosis of the knee treated from 1979 to 1999 were reviewed retrospectively. The radiologic appearance of the joint at presentation was predictive of the outcome. Ninety-two percent of the patients had Stage 1 or Stage 2 involvement (synovitis) with or without bony erosions, but had a normal joint space. Treatment with antituberculous chemotherapy without synovectomy had an excellent or good result in all patients with Stage 1 or Stage 2 disease, and there was no difference in outcome whether the knee was immobilized or mobilized. Patients with Stage 3 and Stage 4 disease who had a narrow joint space (arthritic) at presentation had a fair or poor result. In patients with monoarthritis of the knee with nonspecific histologic features and a negative culture, the differential diagnosis between tuberculosis and pauciarticular juvenile rheumatoid arthritis is problematic. The histologic evaluations of biopsy specimens of the synovium of 25 knees from 25 patients were reviewed for synovial lining hyperplasia. The sensitivity for the 17 knees that subsequently were diagnosed as having juvenile rheumatoid arthritis was only 53%. Deoxyribonucleic acid from 13 consecutive joints was subjected to polymerase chain reaction for Mycobacterium tuberculosis infection with only 40% sensitivity for tuberculosis.