Dorsal root ganglion cells of adult guinea-pigs in vitro were inoculated with herpes simplex virus (HSV). Intracellular recording with a glass microelectrode revealed that HSV-infection caused a marked decrease in membrane excitability of the nerve cells within 24 h, which could be explained as a decrease in Na+ channel activity in the plasma membrane; while changes in other physiological properties (resting membrane potential, membrane resistance and capacitance) remain small. Viral antigens were detected in only 10-15% of the HSV-infected nerve cells. These indicate that the loss of the membrane excitability occurs much earlier than any other change in the HSV-infected nerve cells.