Multidrug-resistant M. tuberculosis in HIV-infected people has not yet been reported in Switzerland, and there have been no nosocomial epidemics as they have recently occurred in the USA. We present the case of a 38-ear-old HIV-infected man who developed disseminated tuberculosis as AIDS-defining disease. Initially he was treated with isoniazid, pyrazinamide and rifampin. Due to the emergence of resistance to isoniazid and streptomycin, ethambutol was added for one month. Later the therapy was changed back to the initial three drugs. The patient responded well to this therapy, but five months later developed a relapse. In addition to the originally diagnosed double-drug resistance, a reduced susceptibility to rifampin appeared. Ethambutol, ciprofloxacin and amikacin were added to the original three-drug regimen. This resulted in rapid clinical improvement, although sputum cultures remained positive for M. tuberculosis two months later. This isolate was resistant to pyrazinamide. For that reason pyrazinamide was replaced by clofazimine. 14 months after diagnosis the patient died of hepatic failure. Because there was a delay in isolation of one week, 37 potentially exposed health care workers were tested by the Mantoux skin test. No conversions were observed. This case report demonstrates that tuberculosis in HIV-infected patients in Switzerland may be caused by multidrug-resistant M. tuberculosis. We propose that until the results of a susceptibility assay are known, a four-drug combination should be used initially in this patient group.