Levofloxacin is a useful quinolone for patients infected with osteomyelitis or tuberculosis. There is little information on the tolerance and safety of levofloxacin in long-term treatment. Fifteen patients (10 men and 5 women) with prosthetic joint infection or chronic osteomyelitis were analyzed. The treatment was levofloxacin (500 mg/d) and rifampicin (600 mg/d). Controls were performed monthly during the treatment, and after that every six months. Problems that were likely related to medication were noted by medical interview. Analyses of hepatic and renal function were performed at each visit. The mean age was 64 years. Ten patients had prosthetic joint infection, two chronic osteomyelitis, two osteosynthetic device infection and one silicone graft infection. Staphylococcus aureus was isolated in eight cases, staphylococcus coagulase being negative in five, and the cultures negative in two cases. The mean duration of treatment was 3.6 months (range 2-6 months). No adverse reactions were observed in seven patients (46%). Occasional digestive symptoms were reported in six patients (40%), and two cases (13%) presented light diarrhea. These patients also took antiinflammatory treatment. Sleeplessness was observed in one patient (6%). Tendinitis or alterations in hepatic function were not observed. In no case was the treatment changed due to adverse reactions. It was concluded that levofloxacin is well tolerated and safe and could be an option for infections that require long-term treatment.