Four children with orbital histoplasmosis caused by Histoplasma capsulatum var. duboisii (one of whom had been unsuccessfully treated with amphotericin-B) were treated with a combination of trimethoprim and sulphamethoxazole (Septrin) and surgical drainage. All patients improved markedly during therapy with resolution of the lesions, and with no recurrence of infection in three patients, 1 year later. The fourth patient was lost to follow-up. Treatment was devoid of side effects. These findings clearly indicate that Septrin could be a safe alternative to amphotericin-B for the treatment of African histoplasmosis, especially in patients presenting with solitary or localized lesions.