The three-dimensional structure of Sindbis virus, an enveloped animal virus, has been determined to a resolution of 35 A by using a common lines procedure to combine cryoelectron micrographs of vitrified particles. The spikes of the virus appear as columnar trimers arranged on a T=4 lattice. The lipid bilayer of the virus envelope is polyhedral and surrounds a smooth T=3 nucleocapsid. Hence, a complete Sindbis virion (molecular weight 46.4 X 10(6)) contains 240 copies of each of the spike proteins and 180 copies of the capsid protein. The arrangement of the spike proteins is complementary to that of the nucleocapsid. Two types of spike-capsid interactions are seen. Spike trimers near the fivefold axes interact tightly with triplets of capsid elements, whereas those on the threefold axes interact more loosely.