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Primary human herpesvirus 6 (HHV-6) and 7 (HHV-7) infections were identified in febrile children by qualitative and quantitative polymerase chain reaction (PCR) assays. Diagnosis was based on the differential detection of viral DNA in peripheral blood mononuclear cells (PBMC), but not in saliva. Six of 41 febrile infants, but none of seven non-febrile controls, were identified with primary infections (three HHV-6, three HHV-7). These children had significantly higher viral loads in PBMC (HHV-6, median 24 213 genomes/10⁶PBMC; HHV-7, median 6 040 000 genomes/10⁶PBMC) than DNA-aemic, saliva PCR positive children (HHV-6, median 1606 genomes/10⁶PBMC, p < 0.01; HHV-7, median 7089 genomes/10⁶PBMC, p < 0.05). Viral DNA was detected in serum by PCR in only 50% of primary infections. All three children with primary HHV-7 infection had febrile convulsions. Thus PCR, including quantitative assays, may identify primary HHV-6 and HHV-7 infections when an appropriate combination of clinical specimens is used.