AbstractThe prototype of the Alphaviruses, Sindbis virus, has a broad host range. In nature, Sindbis virus shuttles from an insect vector to a vertebrate host and back to the insect vector in a complex transmission cycle. Sindbis virus must, therefore, be able to replicate in two biochemically and genetically divergent hosts, invertebrates and vertebrates. In the laboratory, Sindbis grows to high titers in a large variety of cultured cells of both vertebrate and invertebrate origin. Sindbis virus is easily titered for infectivity on several mammalian cell lines as well as certain mosquito cells. Full‐length cDNA clones of several strains of Sindbis virus are available from which infectious RNA can be synthesized, making possible the genetic manipulation of the virus. Transfection of mammalian and insect cells by electroporation has facilitated expression of RNA mutants in the cell lines of choice.