Measles vaccine failure is a well-recognized although not fully understood outcome of immunization. Because seropositivity has generally correlated with both naturally and vaccine-acquired protection, seroconversion is used as an indicator of vaccine efficacy. Failure to seroconvert is classified as primary vaccine failure and is generally attributed to neutralization of the attenuated vaccine virus by persistent maternal antibody in infants younger than 12 months of age1–3 or to inadequate immunization. The latter may be a consequence of storage conditions and/or handling or vaccination in combination with immunoglobulin.4–6 Secondary vaccine failure on the other hand refers to the development of clinically apparent infection despite an immune response to vaccination.7–9 The elicited response may be inadequate to protect against the subsequent inoculum of wild type virus or an initially protective response may wane over time. Although predominantly IgG responses have provided evidence of a secondary response to measles virus upon infection, immunologic data following vaccination or prior to infection have been lacking in the reported cases of secondary vaccine failure. We present a case of vaccine failure despite documented initial seroconversion and persisting measles antibody based on virus neutralization testing.