Congenital human herpesvirus 6 (HHV-6) infection results from germline passage of chromosomally integrated HHV-6 (CI-HHV-6) and from transplacental passage of maternal HHV-6 infection. We aimed to determine whether CI-HHV-6 could replicate and cause transplacentally acquired HHV-6 infection. HHV-6 DNA, variant type, and viral loads were determined with samples (cord blood, peripheral blood, saliva, urine, and hair) obtained from 6 infants with transplacentally acquired HHV-6 and with samples of their parents' hair. No fathers but all mothers of infants with transplacentally acquired HHV-6 had CI-HHV-6, and the mother's CI-HHV-6 variant was the same variant causing the transplacentally acquired congenital HHV-6 infection. This suggests the possibility that CI-HHV-6 replicates and may cause most, if not all, congenital HHV-6 infections.