In the present study, we investigated the effects of bifonazole/urea ointment, a novel topical drug for the treatment of onychomycosis, on the ultrastructure of normal and fungus-infected human toenails by scanning electron microscopy. Nails were treated with the drug ex vivo and compared to untreated controls. During treatment, the corneocyte layers disintegrated, and the structure markedly loosened. After 5 days of treatment, the morphology of fungal cells, found at the undersurface of infected nails, was changed due to the antifungal drug action. The present data demonstrate that by the use of this drug, the agent effectively penetrates the nail plate and affects the fungal cells.