Human herpesvirus-6 (HHV-6) isolates can be classified into variants A and B, and over 95% of people older than 2 years of age are seropositive for either or both variants. However, the prevalence of the two HHV-6 variants is still not defined since the serological methods used at present cannot discriminate one variant from the other. Lymphoproliferative responses to glycine extracted cellular antigens from human herpes-virus-6 (HHV-6) GS strain (variant A)- and Z 29 strain (variant B)-infected T-lymphoid cell lines were examined in healthy Swedish and Japanese adults. Nine of 36 (25%) persons had responses to the GS antigen, while 21/36 (58%) had responses to the Z 29 antigen (P=0.008). Individuals with low anti-HHV-6 IgG titers (< or = 320) were more likely to respond to the Z 29 antigen than to the GS antigen (P=0.006), while there was no difference in those with high anti-HHV-6 IgG titers (> or =1280). Three of 7 Japanese adults had lymphoproliferative responses to the GS antigen compared with 6/29 Swedes (not significant), and 7/7 Japanese had lymphoproliferative responses to the Z 29 antigen compared with 14/29 Swedes (P=0.03). Lymphoproliferative responses were neither related with the presence of HHV-6 DNA nor related with the presence of HHV-7 DNA in peripheral blood cells. These results suggest a higher prevalence of HHV-6 variant B than variant A in both Swedes and Japanese adults, and possibly a difference in either the HHV-6 virus strains and/or the nature of immune response of Swede and Japanese.