Encephalitozoon hellem is a newly described cause of microsporidial keratoconjunctivitis, occurring chiefly in patients with significantly diminished CD4+ T-lymphocyte levels. This disorder is symptomatically disabling and generally recalcitrant to topical antimicrobial therapy. Two homosexual men with E. hellem keratoconjunctivitis diagnosed by Gram stain, transmission electron microscopy, and specific indirect immunofluorescent assay were treated with topical fumagillin (Fumidil B). Both patients had marked symptomatic improvement with reduction of clinical findings. Symptoms and signs recurred with temporary discontinuation of the drug. Both patients, however, remained symptom-free on maintenance levels of topical fumagillin with no evidence of toxic side effects.