BACKGROUND Mycobacterium malmoense (MM) is an atypical mycobacterium responsible for opportunistic infection. The clinical and radiological picture is non-specific. The infection develops most frequently in a dystrophic lung. METHODS A patient of 52 years was admitted with an extensive multifocal pneumonia which later proved to be due to infection with MM. Empirical treatment was started with the combination of rifampicin, isoniazid, pyrazinamide (rifater) and ethambutol (myambutol). Subsequently, cultures showed sensitivity to rifampicin, ethambutol, oxfloxacin, clarithromycin (MIC < 2 mg/l) and rifabutin (MIC < 0.5 mg/l). More than two weeks after the start of treatment, material aspirated at fibroscopy showed the persistence of numerous acid-alcohol fast bacilli, an increase, compared with the original examination, from 5 to 25 per field on day 2, to 20 to 100 per field on day 19. Despite the late addition of clarithromycin there was a progressive deterioration in the pulmonary condition. CONCLUSIONS There is little correlation between the in vivo and in vitro sensitivities of MM to antibiotics. In our patient the progress was unfavourable, even though the mycobacterium was sensitive to the combination of antibiotics used, with the exception of isoniazid that was not tested. In vitro isoniazid does not seem to be active against MM. There is no consensus of opinion on the antibiotic treatment of MM infections.