A review has been presented of the isolation of the first of the viruses in the California encephalitis complex and the sequence of the reported isolations of other members of the group in the United States, Canada, Africa, Europe and Trinidad. Involved are lapses of many years between early isolations in the United States and an interval of essentially twenty years in the San Joaquin Valley of California, despite a constant and increasingly vigorous search. Most viruses of the group have laboratory characteristics quite similar to those of the prototype, but their antigenic mosaic is highly varied suggesting that this virus is quite unstable. In addition to five previously recognized viruses in the group, two of which were from the United States, there now appear to be at least seven antigenic types in the United States in the viruses so far compared in this laboratory. The prototype virus measures about 50 mµ by electron microscopy and is observed only in the cytoplasm of cells. Clinical cases, rarely recognized in previous years, have recently been reported in increasing numbers from many parts of the United States based on serological testing. The first epidemic was recognized in 1964 in Indiana. Virus isolation has been reported from one fatal case of encephalitis; otherwise all virus isolations have been from arthropods, chiefly mosquitoes, and from hares and rabbits. The cycle in nature is probably principally from small mammals to mosquitoes and back to the small mammals, while man appears to be an accidental dead end host. There is no evidence of involvement of birds, an apparently highly resistant group of vertebrates.