A role for human herpesvirus 6 (HHV6) in the neurological complications associated with infection by human immunodeficiency virus (neuro-AIDS) and during multiple sclerosis (MS) is not known. For the present study, an improved PCR and immunofluorescence serology method were applied to sera and cerebrospinal fluid (CSF) from 27 neuro-AIDS, 36 MS and 24 non-inflammatory control patients. HHV6 DNA was present in 30-40% of the cellular CSF from all groups. In the acellular CSF, HHV6 could be detected in four of 36 MS, 2 of 27 neuro-AIDS and none of the control patients. HHV6 IgG was present in one of 27 neuro-AIDS, and one of 36 MS patients. HHV6 IgG was present in all patients. There was no correlation between clinical features and HHV6 PCR findings or HHV6 antibodies. The significance of the present documentation of HHV6 DNA in the acellular CSF from a minority of MS and neuro-AIDS patients remains to be determined.