Short-course chemotherapy of six-month duration with an initial combination of three drugs (isoniazid [H], rifampin [R] and pyrazinamide [Z]) is recommended as the treatment of choice in tuberculosis today. Use of fixed-combination tablet (Rifater) prevents prescription errors by physicians and selective intake by noncompliant patients. It should therefore assist in the prevention of emergence of drug resistance. In a controlled study at a chest hospital in Switzerland involving 261 patients with culture proven tuberculosis, the following two regimens were compared: 1) Six-month therapy (n = 128) with daily Rifater for two months, followed by H and R for four months. 2) Nine-month therapy (n = 133) with H and R daily for nine months, supplemented by ethambutol for the first two months. The two patient groups were comparable except for initial drug resistance (16% vs 8%, p < 0.05). Overall resistance to H was 10%. Five patients had initial resistance to two or more drugs. 227 patients were re-examined 1-8, and on average 4 years after therapy: four patients relapsed after 12, 20, 36 and 90 months. Two patients with initial drug resistance to H later developed resistance to R; both of these, as well as a third relapse patient, were cured with subsequent multi-drug therapy. Despite two and a half years of chemotherapy and repeated surgery, the fourth patient with initial resistance to H and R could not be cured. All relapse patients with initial drug resistance were randomized into the six-month therapy group.(ABSTRACT TRUNCATED AT 250 WORDS)