The DNA sequences for the coding and flanking regions of the type-common glycoprotein-D (gD) genes of herpes simplex virus (HSV) types 1 and 2 have been determined. The resultant protein sequences are approximately 80% homologous. Both gD proteins are 393 amino acids long and both have maintained three identical potential glycosylation sites. Amino acid changes are found throughout the proteins, with the majority of changes located in the amino and carboxyl/termini. Most of the amino acid differences were found to be conservative. Hydropathy analysis, which determines hydrophobic and hydrophilic regions, reveals a remarkable structural similarity between the proteins. Examination of 5' flanking sequences demonstrates extensive DNA sequence homology adjacent to the start of gD gene transcription. In addition, another homologous noncoding region was found 3' to the gD gene. This second homologous sequence is 5' to a 1.6-kb transcription unit.