AbstractTo elucidate the mechanism of heterologous antibody responses to herpes simplex virus (HSV) and varicella‐zostcr virus (VZV) which occur in some patients with HSV or VZV infections, stronger evidence was sought for the existence of cross‐reacting antibodies to these viruses, using antibody absorption procedures. Absorption of sera from initial HSV infections with HSV antigen was found to abolish heterologous antibody titer rises to VZV, as demonstrated in complement fixation, neutralization, and anti‐complement immunofluorescence test systems. In most instances, convalescent‐phase titers to heterologous VZV were reduced by HSV absorption to levels comparable to those in the acute‐phase serum, indicating that cross‐reacting antibodies were, in fact, responsible for the heterologous antibody titer rises. Absorption of convalescent‐phase sera from HSV or VZV patients with homologous antigen also abolished or greatly diminished immunoprecipitating activity with the heterologous antigen, furnishing additional evidence of the existence of cross‐reacting antibodies. Absorption of sera with insolubilized IgG to reremove rheumatoid factor, which was present in a number of the sera studied, had no effect on either homologous or heterologous antibody titer increases. The demonstration of cross‐reacting antibodies to HSV and VZV supports the concept that these two human herpesviruses share