SummaryAmong HIV-positive patients who received treatment for active tuberculosis, thiacetazone has been associated with cutaneous hypersensitivity and recurrent tuberculosis. No controlled trials have investigated the safety and efficacy of thiacetazone-containing regimens compared with alternative regimens among patients with HIV. In a randomised clinical trial of 191 HIV-positive patients with active pulmonary tuberculosis, we examined the safety and short-term efficacy of isoniazid, rifampicin, and pyrazinamide for two months followed by isoniazid and rifampicin for seven months (RHZ) compared with streptomycin, thiacetazone, and isoniazid for two months followed by thiacetazone and isoniazid for ten months (STH). Between May, 1990, and September, 1991, 191 HIV-positive adult Ugandan patients with acid-fast bacilli sputum smear-positive pulmonary tuberculosis (93% confirmed by culture) received either STH or RHZ. Subjects had a standard evaluation that included Mantoux skin test, complete blood count with differential white blood cell count, and chest radiography. After starting therapy, subjects were followed-up over one year for three outcomes: complications of anti-tuberculosis therapy, early sterilisation of cultures, and survival. Of 191 eligible subjects, 90 received STH and 101 received RHZ. The overall one-year survival was similar for STH and RHZ (65% vs 72%), but when controlled for baseline differences in Mantoux reaction size and absolute lymphocyte count, the relative risk of death for STH compared with RHZ was 1·57 (95% Cl 1·0-2·48). Overall, 12 adverse drug reactions occurred in the STH arm (18·2 reactions per 100 person years [PYO]) compared with one in the RHZ arm (1·6 reactions per 100 PYO) for a relative risk of 11·7 (95% Cl 1·52-90·0). 10 cutaneous reactions occurred in the STH arm (15·2 events per 100 PYO) compared with one event in the RHZ arm (1·6 events per 100 PYO) for a relative risk of 9·7 (95% Cl: 1·24, 75·8). A greater proportion of RHZ patients compared with STH patients had sterilised their sputum within two months (74% vs 37%, p<0·001).In developing countries, rifampicin-containing regimens should be given, when possible, to HIV-positive patients to reduce drug toxicity and to prolong survival.