A 14-year-old girl had a granulomatous conjunctival lesion, proven histologically to be malakoplakia. This is the first reported case of malakoplakia arising from conjunctiva, although three others have involved the ocular adnexa. Malakoplakia is a rare disease often associated with immunodeficiency and is characterized by the presence of intracellular inclusions and organisms due to deficient intracellular bacteriolysis. Medical management is difficult because an effective antibacterial agent requires three properties: activity against the organism involved, good intracellular penetration, and the capacity to maintain its effectiveness in the intracellular milieu. Escherichia coli was isolated from a biopsy specimen and from conjunctival swabs. Treatment with systemic ciprofloxacin, which has good intracellular penetration and activity, led to rapid resolution of the lesion. This is the first report concerning the successful use of this drug to treat malakoplakia of any organ.