Human herpesvirus-6 (HHV-6) was recovered at high frequency (greater than 85%) from the saliva of both healthy individuals and those infected with the human immunodeficiency virus (HIV). The level of isolation mirrored the high prevalence of antibodies to HHV-6 found in sera obtained from residents of diverse areas of the world. Seroconversion occurred between 1 and 3 years of age; seroprevalence ranged between 80% and 100% among adults under 40 and decreased to 35% between ages 62 and 88. Serum titres in healthy individuals remained stable during periods of virus shedding. Immune cellular dysfunction in patients was associated with high geometric mean HHV-6 antibody titres. These observations suggest that HHV-6 infection takes place within the first 3 years of life, and strongly implicate oral shedding as a common means of transmission of this newly described herpesvirus.