Despite great progress in measles control in sub-Saharan Africa, measles remains a significant cause of morbidity and mortality in young children. In regions of high HIV prevalence, measles virus transmission may be sustained despite high immunization coverage rates if HIV-infected children are important transmitters of measles virus. Factors potentially contributing to enhanced measles virus transmission by HIV-infected children include an early decline in protective maternal antibody titers resulting in susceptibility to measles at a younger age, and high rates of primary and secondary measles vaccine failure. To evaluate the potential impact of the HIV-1 epidemic on immunity following measles vaccination, we conducted a longitudinal study to compare the primary vaccine failure rate and rate of antibody decline following administration of standard-titer measles vaccine at nine months of age to HIV-infected and HIV-uninfected Zambian children. Our results show that children born to HIV-infected women have lower levels of passively-acquired maternal antibodies to measles virus prior to the age of routine vaccination at 9 months, and HIV-infected children are particularly susceptible to measles in infancy. This finding supports the WHO recommendation to provide the first dose of measles vaccine to HIV-infected children at 6 months. Furthermore, HIV-infected children develop adequate primary antibody responses to measles vaccine in the months following vaccination but lose protective antibody titers by two to three years of age. Mitigating the potential impact of this decreased immunogenicity on the level of population immunity to measles virus was the high mortality rate observed among HIV-infected children. Improved access to antiretroviral therapy will likely improve the survival of HIV-infected children without enhancing protective immunity to measles virus, although this has yet to be investigated. We are working to incorporate our findings into a mathematical model to better understand the impact of the HIV-1 epidemic on measles control strategies and to investigate the immunologic mechanisms for impaired memory B cell responses in HIV-infected children.