A randomized prospective, pilot study was performed to compare the efficacy of oral ciprofloxacin (750 mg or 1000 mg bd) with standard oral antimicrobial therapy (rifampicin plus doxycycline) in the treatment of acute infection with Brucella melitensis. All antimicrobial drugs were administered for 42 days. Although all patients responded rapidly, five of the six patients receiving ciprofloxacin relapsed following cessation of therapy. There were no relapses among the patients who received doxycycline/rifampicin. Despite its in-vitro activity against B. melitensis (MIC 0.5 mg/l), ciprofloxacin, administered twice daily, does not appear to constitute adequate therapy for acute brucellosis.