Groups of 5‐week‐old BALB/c mice were immunized intraperitoneally with approximately 10 μg of purified alum‐precipitated glycoprotein gB or gD of either herpes simplex virus type 1 (HSV‐1) or type 2 (HSV‐2) origin. Control mice received injections of alum‐precipitated 1 % bovine serum albumin (BSA). Following a second immunization 4 weeks later, seroconversion was confirmed by demonstrating the presence of glycoprotein‐specific antibody by immune precipitation. All animals were challenged with lethal doses of either HSV‐1 or HSV‐2 by footpad inoculation and assessed for acute virus‐induced neurological disease and the development of ganglionic latency. Whereas 70% of control (BSAimmunized) HSV‐ 1 ‐infected animals developed ascending myelitus and died, 100% of mice immunized with either gB‐1, gB‐2, gD‐1, or gD‐2 antigens remained free of clinical illness and survived HSV‐1 challenge. In contrast, gB‐1 or gB‐2‐immunized mice were not protected against acute HSV‐2‐induced neurological disease and showed a mortality rate of 60–90% (equivalent to that seen in controls), although mean survival times were prolonged. However, significant protection against HSV‐2 challenge was observed with gD‐1 or gD‐2 immunization. When sacral ganglia were removed from surviving mice 9–12 months after virus challenge, latent virus was detected in all gB‐ or gD‐immunized animals, although the extent of latent infection was restricted. These results provide evidence that glycoprotein gD might be superior to glycoprotein gB as an immunogen for the control of acute HSV‐1 and HSV‐2 neurological disease in mice. However, neither glycoprotein prevents ganglionic latency, the source of virus for recurrent herpesvirus infections.