To study the mechanisms of protection to Hantaan virus(HV) and the effects of HV on immune response, viral antigen, antibody, mitogen response and natural killer cell activity were periodically observed in 6-8 weeks old ICR mice inoculated with 10' PFU/ml of HV by intraperitoneal route. 1. Immunofluorescent IgG anti-HV antibodies appeared on day 8 and then titers increased rapidly, to reach 1: 512 on day 20. Thereafter titers continued to rise slowly until day 32 (last day of measurment). Viral antigens in brain, lung, heart, liver, kidney, spleen were not detected by direct immunofluorescent stain. 2. On 1,4,8,12,16 days after inoculation, spleen cells were removed and stimulated in vitro in the presence and the abscent of Con-A or LPS. The responsiveness to Con-A and LPS was compared with the ratio of virus inoculated to that of control(virus/control). The responsiveness to Con-A were slightly suppressed on day 8, 12(0.8+0.2) snd then increased at day 16(1.3+0.3). The responsiveness to LPS were continuously increased until day 12(2.2+ 0.3) thereafter decreased. 3. Natural killer cell activity of spleen cells to YAC-1 target cells (E: T=50: 1) were increased on day 2 and 4 (47+12%, 50+9%), and then decreased to normal level on day 8 (27+6%).