PURPOSE To describe a case of seronegative West Nile virus (WNV) meningoencephalitis definitively diagnosed with ophthalmologic examination and confirmatory repeat laboratory testing. DESIGN Diagnostic case report. METHODS A patient with negative serologic testing for severe viral meningoencephalitis presented with photophobia and blurred vision 2 months after initial presentation. RESULTS Examination revealed all the classic ocular findings of WNV. Repeat serologic testing confirmed positive titers for WNV. CONCLUSIONS WNV may initially present as a severe meningoencephalitis with negative serology. Ophthalmic examination, particularly in symptomatic patients, may help with diagnosis. The ophthalmologist may play a critical role in evaluation of possible WNV meningoencephalitis.