The replication of herpes simplex virus (HSV) was studied in BSC1 cells cultured in the presence of various concentrations of 2-deoxy-d-glucose. At all concentrations tested, the yield of infectious virus was inhibited to a greater degree than the yield of physical particles, while the percentage of the total particles which were enveloped remained constant. Analysis of HSV-induced glycoproteins on SDS-polyacrylamide gels (SDS-PAGE) indicated that as the concentration of 2-deoxy-d-glucose increased, there was a decrease in the apparent molecular weights of the viral glycoproteins. Analysis on SDS-PAGE of the viral-induced proteins indicated no significant alterations with the exception of an additional component detectable only in HSV-infected cultures containing the higher concentrations of 2-deoxy-d-glucose. Preliminary SDS-PAGE analysis indicated that 2-deoxy-d-glucose is incorporated into the HSV-induced glycoproteins.