The surface antigenic make-up of 10 HHV-6 isolates from cases of infantile disease was analyzed by immunofluorescence assay with 5 monoclonal antibodies (Mabs). Three Mabs were directed to glycoproteins (gps) expressed in cells infected with the HHV-6 variant A prototype GS, and 2 to gps expressed in cells infected with the HHV-6 variant B prototype Z29. Of the 10 viral isolates, all belonging to HHV-6 variant B, 9 showed a similar Mab reactivity, while 1, from a case of gastroenteric illness, differed widely from the others. The HHV-6 isolates studied also differed from the variant B prototype Z29 for the absence of reactivity to one of the Mabs. The choice of the HHV-6 new isolates as variant B prototypes is recommended.