Mature mouse spinal cord-ganglion cultures, which contain both peripheral and central nervous system as one unit, were infected with herpes simplex virus type 1 (HSV 1) or type 2 (HSV 2) and observed by bright field microscopy for up to 72 hours. There was degeneration of both central and peripheral myelin in cultures infected with either virus, but the pattern of peripheral myelin degeneration associated with HSV 1-infected cultures was differrnt from that in HSV 2-infected cultures. Type 1 was charcterized by focal dilatations; type 2 by "sausage-shaped" swellings, and the cytopathic effect of HSV 2 both began (6 hours p.i.) and was completed (36 hours p.i.) earlier than in cultures infected with HSV 1 (12 hours and 48 hours p.i. respectively). In central nervous tissue, the apperance of degenerating myelin after infection with HSV 1 was indistinguishable from that in HSV 2-infected cultures, but the rate of myelin loss was greater in cultures infected with the type 2 virus. Evidence is presented which suggests that, at least in the peripheral nervous system,myelin degeneration did not appear to be dependent on neuronal or axonal dysfunction or death, but was a direct result of virus infection.