Mice infected with Brucella melitensis were treated with azithromycin or roxithromycin at a dose of 50 mg/kg/day i.p. alone and in combination with streptomycin 75 mg/kg/day for 14 days. Streptomycin at this dose was previously documented to be ineffective against murine brucellosis. Azithromycin- and azithromycin/streptomycin-treated animals demonstrated a significantly better cure rate than controls. Therapy failure was observed in all mice treated with roxithromycin 50 mg/kg/day i.p. alone or in combination with streptomycin 75 mg/kg/day. Our findings demonstrate that azithromycin cures experimental murine brucellosis and may be an effective alternative in the therapy of human brucellosis.