We evaluated ciprofloxacin, ofloxacin and pefloxacin regimens for the treatment of chronic osteomyelitis due to Gram-negative multiresistant organisms. The study was open, nonrandomized and included 28, 21 and 16 patients, respectively. The 4-fluoroquinolone regimens were 1000 mg, 400 mg and 400-800 mg bd, for a mean duration of 137, 163 and 134 days, respectively. Pseudomonas aeruginosa was the most common pathogen, isolated in 33 individuals. Patients were followed clinically, bacteriologically and radiologically during treatment and for 2-5 years after discontinuation of therapy. Clinical outcome at the end of therapy was successful in 79%, 81% and 75%, improvement occurred in 11%, 10% and 19%, and the failure rate was 11%, 10% and 6%, while 11%, 5% and 6% relapsed, respectively. At the end of follow-up the bacterial eradication rate was 68%, 76% and 69%, respectively. Fluoroquinolone resistance emerged in 18%, 19% and 13% of ciprofloxacin, ofloxacin and pefloxacin recipients, respectively. The newer quinolones were safe and well tolerated and should be considered as the contemporary treatment of choice for chronic Gram-negative osteomyelitis, particularly whenever P. aeruginosa is implicated.