We have shown in Arkansas that 9 months of therapy with isoniazid (INH) and rifampin (RIF) can achieve lasting success in 95% of cases with sputum-smear-positive pulmonary tuberculosis. It seemed likely that when the tubercle bacilli were less numerous, i.e., could not be seen on microscopy, less therapy would suffice. Thus, in January 1980, we began giving only 6 months of treatment to patients in whom at least one sputum culture showed M. tuberculosis but at least three sputum smears showed no organisms. The regimen for adults is INH 300 mg and RIF 600 mg daily for 1 month followed by INH 900 mg and RIF 600 mg twice weekly for another 5 months. To date, 286 patients with an average age of 68.2 yr have been treated in this manner. Associated medical conditions were present as "risk factors" in 23.7%. The full course of therapy could not be completed in 75 patients (26.2%), largely because of side effects of the drugs and non-TB deaths in this group of elderly patients. Side effects of the drugs requiring change of drug(s) occurred in 33 patients (11.5%), but major side effects occurred in only eight (2.8%), four (1.4%) with toxic hepatitis and four with hematologic toxicity. The side effects in 25 patients (8.7%) were not life-threatening and were due to drug intolerance. Treatment failed during therapy in only one patient. The full 6-month course of therapy was completed by 211 patients. During follow-up from 3 to 107 months (median, 45 months), five of 211 patients (2.4%) relapsed, all with drug-susceptible organisms.(ABSTRACT TRUNCATED AT 250 WORDS)