Short-course, largely twice-weekly chemotherapy for tuberculosis was introduced in the United States for treatment of adults with pulmonary disease by the Arkansas State Department of Health in 1976. Since 1977, 50 children with tuberculosis have been treated with rifampin, 10 to 20 mg/kg, and isoniazid, 10 to 20 mg/kg daily for one month followed by 10 to 20 mg/kg of rifampin and 20 to 40 mg/kg of isoniazid twice a week for another 8 months. Ages ranged from 4 months to 15 years with a median age of 3 years. A presumptive diagnosis of tuberculosis was made on the basis of 10 mm or more of induration to 5 TU of purified protein derivative and a chest film or other findings compatible with tuberculosis. Three children had extrapulmonary disease (two had cervical adenitis, one had tuberculosis arthritis). Of the 47 children with pulmonary disease, 32 were asymptomatic. The results were excellent. Symptoms cleared in 1 to 2 months. Most pulmonary infiltrates had cleared by 10 months, but hilar adenopathy rarely cleared in less than 2 years. Drug toxicity occurred in only one patient (vomiting of rifampin). This treatment appears to be safe, effective, inexpensive, short and simple enough to ensure cooperation or to allow personnel to administer drugs directly to children from socially disorganized families.