A 50-year-old woman allergic to penicillin with early latent syphilis was treated with two courses of doxycycline. Ten months after diagnosis, she had no evidence of serologic response. A lumbar puncture demonstrated asymptomatic neurosyphilis. Penicillin desensitization was performed and she was successfully treated. This case re-emphasizes the need for close serologic follow-up in patients with latent syphilis.