For HCV, it has proved extremely difficult to Cryptochlorogenic-acid visualize the virus in infected cells, but an HCV-like particle model based on the production of the viral structural proteins has demonstrated that HCV also buds at the ER membrane. However, the mechanism leading to the release of flavivirus virions from the infected cells remains poorly documented. It is believed that virions transit from the ER lumen to the cell surface via the secretory pathway, but this process is probably very rapid and has yet to be documented by microscopic approaches. In this study, we took advantage of the development of an optimized system of chimeric YFV/DENV production for vaccine purposes to study this phenomenon. We also used correlative microscopy, a powerful method for targeting and studying rare structures or rapid biological events. Rather than using the well described correlative light-electron microscopy technique, we established a new method for this study: correlative scanning electron microscopy-transmission electron microscopy. This new type of correlative microscopy, based on the detection of cells of interest by scanning electron microscopy, for further investigation by transmission electron microscopy, made it possible to visualize the release of a flavivirus at the cell surface. Our morphological data suggest that individual viral particles are secreted from infected cells in small secretory vesicles and that this new correlative microscopy method would be useful for deciphering other biological processes. The mechanism underlying flavivirus release from the host cell remains unclear. As these viruses accumulate in dilated ERderived cisternae, it has been suggested that they may be released by the exocytosis of these large virion-containing vacuoles and/or as individual viral particles in secretory vesicles. However, it has been also suggested that WNV could be released by a budding at the apical surface of the plasma membrane. We report here the first visualization, by SEM, of a chimeric flavivirus at the surface of an infected cell. Our SEM photographs of chimeric YFV/DENV-infected cells demonstrate that the viral particles are not released in clusters in a polarized area of the cell. Instead, they are released individually and evenly over a large surface of the cell. The scarcity of chimeric virus-covered cells suggests that this phenomenon is Isoacteoside short-lived, probably accounting for the difficulties encountered in a empts to observe the release of viral particles in ultrathin sections analyzed by TEM. This led us to develop an original method �� CSEMTEM, for correlative scanning electron microscopy-transmission electron microscopy �� for identifying virus-covered cells and selecting them precisely by SEM. These cells were then embedded in resin and sectioned, for further analysis by TEM. The ultrastructure of the cells that had previously been prepared for SEM analysis was found to be very well preserved when these cells were analyzed by TEM. No major difference could be found between these cells and those prepared by regular TEM protocols. The major difference concerned the chimeric viral particles at the cell surface, which appeared as extremely dense particles with a diameter of 60 to 70 nm.