The serological response of paediatric oncology patients to human herpesvirus-6 (HHV-6) was investigated at presentation and during treatment. Sera from 66 patients presenting with malignancy and 66 controls were examined for anti-HHV-6 IgG by indirect immunofluorescence test (IFA) and enzyme linked immunosorbent assay (ELISA), and for anti-HHV-6 IgM by IFA. Serial samples from 45 children on chemotherapy were examined for anti-HHV-6 IgG by ELISA and sera from selected patients on chemotherapy were examined for IgM by IFA. The response of these patients to four other herpesviruses was also investigated. Ninety percent of presenting patients and controls were IgG positive for HHV-6 by IFA and ELISA. Anti-HHV-6 IgG as measured by the HHV-6 ELISA index declined over time in patients on chemotherapy. Two presenting controls and one leukaemic child with a primary cytomegalovirus seroconversion were anti-HHV-6 IgM positive. In the patient group seropositivity to herpesviruses (types 1-6) increased with age, the mean age of those with IgG to HHV-6 alone was 3.7 years compared to 6.8 years for those with antibodies to all five viruses. At the time of presentation paediatric oncology patients have a similar serological response to HHV-6 as age-matched controls and this IgG response wanes with treatment. Whether this is significant in terms of viral pathogenicity is not known and will require investigation of viral activity in these patients.