We compared susceptibility of inbred mouse strains against intracerebral as well as peripheral challenge of a flavivirus, Japanese encephalitis (JE) virus, and the results were summarized as follows: (1) Seven inbred mouse strains (C3H/He, C57BL/6, BALB/c, AKR/N, NC, NZB, DBA/2) could be classified into following 3 groups by their mortality and infection rate when they were subcutaneously challenged with a wild JE virus strain isolated from field-caught mosquitoes at a single passage in mouse (B18AM, B-1): (1) high mortality and high infection rate (C3H/He, C57BL/6, AKR/N), (2) low mortality but high infection rate (BALB/c, NC, NZB), and (3) low mortality and low infection rate (DBA/2). The DBA/2 strain showed lowest mortality and infection rate with statistically significant difference with other strains. (2) Three inbred mouse strains (C3H/He, C57BL/6, BALB/c) were peripherally challenged with following 6 different wild strains of JE virus: mosquito origin after a single passage in mouse (B-1); mosquito origin after 30 passages in mice by subcutaneous inoculations (BP-30), mosquito origin after 30 passages in mice by intracerebral inoculations (BB-30); human origin after a single passage in mouse (JaNH180,J-1); human origin after 30 passages in mice by subcutaneous inoculations (JP-30); human origin after 30 passages in mice by intracerebral inoculations (JB-30). Survival of these inbred mice showed curves, with statistical difference among mouse strains. Anti-JE ELISA antibody titers in survived mice were lowest in BALB/c among 3 inbred mouse strains for all JE virus strains used to the challenge experiment. The result indicated that BALB/c would be a suitable host to study inapparent JE virus infection which is frequent among humans exposed to JE virus. (3) Male mice showed higher mortality than females when 4 weeks old mice were peripherally challenged by JE virus, and the difference was statistically significant. The results as a whole indicated that the susceptibility of mice to JE virus is under the control of genetic factors.