To investigate age-dependent differences in hantavirus-specific CD8(+) T-cell responses, mice were inoculated with 0.1 50% newborn mouse lethal dose of Hantaan virus (HTNV) at 0, 3, 7, 14, or 35 days after birth. HTNV-specific CD8(+) T cells producing gamma interferon (IFN-gamma) were measured on day 30 after HTNV inoculation. Although no IFN-gamma-producing HTNV-specific CD8(+) T cells were detected in most of the mice inoculated with HTNV on day 0 after birth, most mice inoculated at 3, 7, 14, or 35 days had HTNV-specific CD8(+) T cells. The production of tumor necrosis factor alpha (TNF-alpha) by IFN-gamma-producing CD8(+) T cells and the cytotoxic activity against HTNV-infected target cells were similar in immature and adult mice. However, the number of IFN-gamma-producing HTNV-specific CD8(+) T cells was significantly less in mice inoculated with HTNV at 3 days than in older mice. In addition, a strong correlation between HTNV persistence and a lack of HTNV-specific CD8(+) T cells was observed. These results suggest that mice over 7 days old have the ability to induce functional HTNV-specific CD8(+) T-cell responses that are indistinguishable from the responses of adult mice, and that HTNV-specific CD8(+) T cells are important for clearance of HTNV.