The morphogenesis of yellow fever virus replication was examined in infected Vero cell cultures. Penetration and uncoating occurred by endocytosis with the formation of coated vesicles, similar to that demonstrated for other enveloped and unenveloped viruses. Inclusion bodies associated with newly formed nucleocapsids were evident in the perinuclear region during the growth cycle. No evidence of RNA synthesis in the vicinity of the inclusion bodies was obtained by autoradiography, suggesting that genome replication and assembly of viral nucleocapsids occur at separate cytoplasmic sites. An excessive proliferation of membrane-bound organelles involving both vacuoles and endoplasmic reticula was the most striking feature of virus-infected cells late in infection. No morphological changes in the appearance of nuclei or mitochondria were detected. Virus release appeared to occur by movement of nascent virions through the proliferated endoplasmic reticula followed by exocytic fusion of virus-containing vesicles with the plasmalemma. A possible mechanism whereby the internal nucleocapsid acquires an outer envelope is discussed.