The African strain of chikungunya virus was used to infect newborn mice, and the central nervous system was examined in the electron microscope. Previously, it was shown that, with this virus strain, histological changes in suckling mice consisted primarily of necrosis of neurons in the cerebral cortex and spinal cord. In the present study, ultrastructural changes were found only in the cerebral cortex and spinal cord. Electron-dense particles were seen in the extracellular spaces of the neuropil and within axon fibers. A subtle change in the texture of the cytoplasmic substance and alterations of the endoplasmic reticulum were observed in neurons and glial cells. As with tissue culture cells, the endoplasmic reticulum appeared to be the main organelle involved in virus replication. The close association of electron-dense particles with this membranous structure and the presence of mature virus particles within the endoplasmic reticulum corroborated the findings in tissue culture. The viral core is apparently assembled at the endoplasmic reticulum, and the viral coat is formed from the cellular membrane, which is penetrated by the virus.