The developmental sequence of a neurotropic strain (JHM) of mouse hepatitis virus was examined by transmission electron microscopy and immunocytology. The nucleo-protein core of this coronavirus, which contains RNA of positive polarity and is helical in configuration, becomes incorporated into enveloped particles in the same manner as the nucleocapsids of the orthomyxo- and paramyxoviruses. However, JHM virus is assembled intracellularly by budding at surfaces of smooth membranous vacuoles. A comparison of JHMvirus replication in L2 and 17C1-1 cell lines revealed that L2 cells undergo more rapid cytopathology and cease virus production much sooner than 17C1-1 cells. In L2 cells the accumulation of core material appears to continue after the abrupt cessation of virus assembly. This is evident by the massive cytoplasmic accumulation of structures resembling nucleocapsids, which react with hybridoma antibody to the nucleocapsid antigen as demonstrated by the immunoperoxidase procedure. The current findings are consistent with our previously published demonstration, using cells of neural and other deviation, of the fundamental role of the host cell type in regulating the replication and expression of coronaviruses.