The extent of antibody cross-reactivity of pooled antisera from rhesus monkeys, baboons, African green monkeys, langurs, sooty mangabeys and humans to 6 alphaherpesviruses (herpes B virus, herpes papio 2, simian agent 8, langur herpes virus and herpes simplex 1 & 2) was examined by two types of enzyme linked immunosorbent assays, an antibody capture assay (tELISA) and an antigen capture assay (dELISA). Percent cross-reactivity was calculated for each serum by comparison of the homologous reaction (100%) to the reaction with heterologous viruses. Comparison of the immunological reactivity of the mangabey antiserum pool to the panel of alphaherpesviruses indicated that these antibodies were induced by a yet unidentified alphaherpesvirus. In general, monkey sera were more cross-reactive to monkey herpesviruses than to human herpesviruses. However, the extent of cross-reactivity of monkey sera to human herpesviruses was relatively lower than the cross-reactivity of human sera to monkey herpesviruses. Because of this phenomenon of "one-way" cross-reactivity that was also observed within the group of simian herpesviruses, it was difficult to rank the immunologic distances between the viruses in absolute terms.