Technical Abstract: A recent handful of studies have linked baculovirus infection with the induction of heat shock proteins, a highly conserved family of cytoprotective proteins. Here, we demonstrate baculovirus-stimulated upregulation of hsp70 transcription in the natural host, Helicoverpa zea. Larvae lethally infected with the Helicoverpa zea single nucleopolyhedrovirus (HzSNPV) accumulated hsp70 transcripts throughout the 72 hour course of infection in the midgut, hemocytes, and fat body. While a maximal 20-fold induction of hsp70 was noted in the midgut and hemocytes, by 72 hours post infection, hsp70 transcription in the fat body of infected larvae was greater than two orders of magnitude over that of mock-infected larvae. These results were largely mirrored in cultures of infected cells, and a potentiation effect was observed in cells that were both heat shocked and infected. In contrast, neither Spodoptera frugiperda multiple NPV nor ultra-violet inactivated HzSNPV were able to stimulate hsp70 transcription in these experimentally non-permissive larvae and cell culture, respectively. Taken together, this report documents baculovirus-mediated upregulation of hsp70 in the natural host, and demonstrates the requirement for productive infection for hsp70 induction in vitro and in vivo.