Varicella-zosterer virions present in infected cells or in a cell-free state were freeze-dried without loss of structural integrity of infectivity. Generally, yields of greater than 5 log10 foci/ml (infected cells) or greater than 4 log10 PFU/ml (cell-free virus) were recovered from varicella-zoster virus-infected human melanoma cells both before and after lyophilization in phosphate-buffered media containing 0.1-1.0 M sucrose. Virus frozen in solutions lacking sugar had little or no residual infectivity after vacuum sublimation was completed. Visualization by electron microscopy demonstrated large numbers of enveloped virions in the virus preparations lyophilized in media containing sucrose; in marked contrast, virus subjected to freeze-drying in buffered solutions without sugar consisted mainly of naked nucleocapsids. Water analyses by Karl Fischer titration suggested that residual moisture retained by sugar prevented disenvelopment of the varicella-zost virion.