The DNA sequence encoding the complete HSV-1 glycoprotein G (gG) was inserted into a baculovirus transfer vector and recombinant viruses expressing gG were isolated. Three gG-related recombinant baculovirus expressed peptides of 37, 42, and 44 kDa were detected by Western blotting using monoclonal antibody to gG. The 42- and 44-kDa species were susceptible to tunicamycin, Endoglycosidase H (Endo-H), and N-glycosidase F (PNGase F) treatments, suggesting that they were glycosylated. Although only very low levels (approximately 1:10) of HSV-1-neutralizing antibody were produced in mice vaccinated with the baculovirus gG, these mice were partially protected from lethal challenge with HSV-1 (75-78% survival) and this level of protection was highly significant (P = 0.002). This is the first report to show that vaccination with HSV-1 gG can provide mice with any level of protection against lethal HSV-1 challenge.