The development of enterovirus specific T-cell and antibody responses were examined in a cohort of 60 healthy infants at the ages of 3, 6, 9, and 12 months. By the age of 6 months, 68% of the infants had developed T-cell responses against enterovirus antigens by lymphocyte proliferation test, whereas only 30% had serological evidence of an enterovirus infection. By this age, only 7% of the infants had adenovirus specific T-cell responses and 3% had serologically verified adenovirus infection. Enterovirus specific T-cell responses correlated with the lack of enterovirus antibodies in cord blood and the number of sibs reflecting protection by maternal antibodies and the rate of exposures, respectively. T-cell responses cross-reacted between different enterovirus serotypes. The results show that enterovirus infections occur frequently in infancy and induce T-cell immunity. Cellular immunity may be a more sensitive indicator of neonatal enterovirus infections than antibodies.