The effectiveness of treatment of human brucellosis caused by Brucella melitensis with ciprofloxacin alone was investigated in a prospective nonrandomized study. Subjects with central nervous system involvement, endocarditis, or severe renal dysfunction; children under 16 years of age; and pregnant women were excluded from the study. Of 19 patients, 16 completed the study; 7 were diagnosed as having acute systemic brucellosis, and 9 had acute brucella arthritis-diskitis. A rapid response to ciprofloxacin was seen in all 16 patients, but the blood cultures of 1 patient remained positive and the treatment was changed. During a 104-week follow-up period, 4 of the 15 responding patients relapsed or were reinfected within 8 to 32 weeks after completion of therapy. We conclude that treatment with ciprofloxacin alone, although effective for the acute symptoms, is associated with an appreciable rate of relapse; therefore, it should be given with other agents for treatment of brucellosis.