A mouse hepatitis virus, strain JHM, grown on DBT cell culture was inoculated intranasally into ICR-SLC weanling mice, and histopathological lesions were studied in relation to viral growth. In the spleen virus titer reached a peak of 10(3) PFU/0.2G 48 H after inoculation, and later it decreased gradually. No virus was detected from the liver throughout the experiment, while some early inflammatory reactions appeared in the spleen and liver without any further development. At 48 h postinoculation there existed degeneration and necrosis in the nasal mucosa and submocosa. In the brain and spinal cord active viral growth was seen at 48 h postinfection or later. In the olfactory bulb mitral cells were also affected with accumulation of glial cells and some meningitis. At 72 to 96 h postinoculation, degeneration of neurons and glial cells were remarkable in the tructus olfactorius, cortex of lobus piriformis, septa pellucidum and commissura anterior accompanying meningitis. At 120 h postinfection, pyramidal cells in the hippocumpus were also degenerated and necrotized, and nodular proliferation and collapse of glial cells, small foci of demyelination and perivascular cuffing were seen in the interbrain. At 144 h postinoculation or later, the lesions developed through the whole brain including the pons and medulla oblongata as well as spinal cord. Brain virus titers showed 10(5) PFU/0.2g at 120 h and 10(4) PFU/0.2g at 144 h postinfection. In mice surviving at 168 hr after inoculation severe demyelinating lesions were observed despite of a decreased virus titer. These findings suggest that intranasally inoculated virus might invade the olfactory bulb through the tractus olfactorius and then produce necrotizing lesions, extending later towards the posterior parts of the central nervous system.