Core particles of reovirus type 3 Dearing (T3D) crystallized in the face-centered cubic space group F432 with dimensions of 1270 A along each edge of the unit cell. Core particles of reovirus type 1 Lang (T1L) did not crystallize. Experiments with core particles derived from 27 different T1L x T3D reassortant viruses indicated that the L2 genome segment determined the capacity of cores to crystallize. This finding indicates important differences in the surface topography of the L2-translation product, the lambda 2 protein, of these two isolates, and suggests that important crystal contacts are mediated by this protein. These data are used to generate a model of the packing of reovirus core particles within the unit cell.