BACKGROUND: Immune responses are complex traits influenced by genetic and environmental factors. We previously reported that genetic factors control early antibody responses to vaccines in Gambian infants. For the present study, we evaluated the determinants of the memory phase of immunoglobulin G (IgG) responses. METHODS: Antibody responses to tetanus toxoid (TT), measles vaccines, and environmental antigens (total IgG levels) were measured in 210 Gambian twin pairs recruited at birth. Intrapair correlations for monozygous and dizygous pairs were compared to estimate the environmental and genetic components of variations in response. RESULTS: In contrast to antibody responses measured in infants at age 5 months, 1 month after immunization, no significant contribution of genetic factors to anti-TT antibody and total IgG levels was detected at age 12 months. Genetic factors controlled measles antibody responses in 12-month-old infants, which indicates that the increasing influence of environmental determinants on anti-TT responses was not related to the older age of the children but, rather, to the time elapsed since immunization. Environmental factors also predominantly controlled affinity maturation and the production of high-avidity antibodies to TT. CONCLUSIONS: Genetic determinants control the early phase of the vaccine antibody response in Gambian infants, whereas environmental determinants predominantly influence antibody persistence and avidity maturation.