Human herpesvirus 6 (HHV-6) is a recently identified lymphotropic herpesvirus, which has been isolated from patients with acquired immunodeficiency syndrome (AIDS) or lymphoproliferative diseases. Two variants A and B of HHV-6 have been described, variant B being more common in children with exanthema subitum. HHV-6 infection was studied in cases of AIDS-associated non-Hodgkin's lymphoma (NHL), and in three control populations in order to evaluate the possible etiological role of HHV-6 in this lymphoproliferative disease. Tumor specimens from various organs were obtained from 27 patients with AIDS-associated NHL and 20 human immunodeficiency virus (HIV)-seronegative patients with NHL. Lymph node specimens were obtained from four HIV-seropositive and nine HIV-seronegative patients with lymph node follicular hyperplasia. A specific polymerase chain reaction (PCR) was used to detect HHV-6 DNA. Subsequently HHV-6 variant was identified by using variant-specific PCR. Human cytomegalovirus (CMV) infection was detected in parallel by means of specific PCR. HHV-6 DNA was detected in 12 of 27 tumor tissues (44%), including 8 of 15 lymph node specimens (53%) from patients with AIDS-associated NHL. The corresponding values in HIV-seronegative patients with NHL were 35% (7/20) and 36% (5/14), respectively. Lymph node specimens were positive for HHV-6 in two of four (50%) HIV-seropositive and five of nine (55%) HIV-seronegative patients with follicular hyperplasia. Variant A was detected in two cases of AIDS-associated NHL, variant B in one case, and both variants in six cases. The distribution of HHV-6 variants exhibited a similar pattern in the three control groups.(ABSTRACT TRUNCATED AT 250 WORDS)