Core gene deletion mutants of hepatitis B virus (HBV) have been identified in adults. Because the acquisition of HBV occurs mainly in infancy and childhood in hyperendemic areas, this study aimed to learn the temporal profile of such mutants in children with chronic HBV infection. We have followed up 365 HBV-infected children for more than 10 years and screened out HBV core gene deletion from their sera. Serial serum samples of positive cases were subjected to HBV-DNA nucleotide sequence analyses and quantification. Deletion mutants were found in 18 of the 365 patients (4.9%). Most cases (15 of 18) with deletion mutants heralded hepatitis B e antigen (HBeAg) seroconversion phase, while the other cases (3 of 18) remained in HBeAg-seropositive phase. Deletion mutants disappeared after HBeAg seroconversion except in 1 child. Decreased HBV-DNA levels accompanied deletion mutants for those who finally underwent HBeAg seroconversion, but the HBV-DNA level did not decline if there was no seroconversion. Deletion mutants were not associated with a particularly high peak liver enzyme. Core gene deletion mutants could appear as early as the age of 5. The duration of their appearance was 0.5 to 5 years. Horizontal rather than perinatal transmission of HBV was a favorable factor for these mutants to develop. Deletion fragments were located in the middle part of core gene. The emergence of the mutants was likely the result of host-viral interaction and mostly signified HBeAg seroconversion within 1 year. Core gene deletion mutants appeared preferably in children acquiring HBV by horizontal transmission.