Treatment of childhood brucellosis is controversial and is currently dependent on inclusion of aminoglycoside antibiotics which are both costly and potentially toxic. Hence an alternate mode of therapy preferably dependent exclusively on oral agents is desirable because this decreases medical cost. In this study we prospectively treated 113 children with a combination of two oral agents, trimethoprim-sulfamethoxazole (10 to 12 mg/kg trimethoprim, 50 to 60 mg/kg sulfamethoxazole and rifampin 15 to 20 mg/kg in two divided doses for 6 weeks. The treatment was well-tolerated and all patients responded by defervescence of fever and resolution of all symptoms within 1 to 3 weeks. Relapse after 6 months occurred in four children all of whom responded to repeat therapy by the same agents. We conclude that the combination of trimethoprim-sulfamethoxazole and rifampin is both cost-effective and safe for the treatment of childhood brucellosis.