We compared cytomegalovirus (CMV)-specific interferon-gamma (IFN-gamma), interleukin 2 (IL-2), and CD154 CD4(+) T cell responses of infants to those from chronically infected adults and from children aged 4-5 years. Magnitudes of the responses were similar, although coexpression of IFN-gamma plus CD154 occurred more than coexpression of IFN-gamma plus IL-2 or IL-2 plus CD154. Responses remained constant during infancy, although the proportion of IFN-gamma-producing cells increased from infancy to adulthood. Most responding cells in infants were undifferentiated (i.e., CD27(+)CD28(+)), although IFN-gamma-producing cells were disproportionately CD27(-). By 12 months after diagnosis, viremia was rarely detectable, indicating that CMV was controlled despite the slow development of CMV-specific CD4(+) T cell responses.