We designed experiments to assess the effects of binding of the HSV-2 Fc receptor (FcR) to purified rabbit nonimmune IgG and purified Fc. Purified Fc (75 micrograms) or nonimmune IgG (100 micrograms) when bound to HSV-2 did not reduce infectivity but did protect the virions against thermal inactivation at 37 degrees C. However, preincubation of these two reagents with HSV-2 virions significantly protected against neutralization by specific anti-HSV-2, F(ab')2 purified rabbit antiserum. The blockage of neutralization and protection against thermal inactivation afforded by FcR-Fc interaction on HSV-2 virions provide a tenable mechanism to explain viral persistence in an immune host.