Baby-hamster kidney cells were treated with unspecific and phosphatidylinositol-specific phospholipase C (PI-PLC) prior to infection with herpes simplex virus type 1 or 2. Subsequent to PI-PLC treatment, a 30% reduction of infectivity and receptor binding was observed for type 1 virus, while type 2 was unaffected. Treating the cells with unspecific phospholipase C did not affect subsequent infection with either virus. Treatment of the virus particles with the unspecific phospholipase reduced its infectivity, probably due to loss of the viral envelope. PI-PLC treatment of virus particles did not have any such effect on virus infectivity.