OBJECTIVE: To study the value of antiviral therapy for infectious monocytosis (IM) in children by comparing the near-term therapeutic efficacies and long-term follow-up results in children with this disorder between receiving antiviral therapy or not. METHODS: The medical data of IM children between 1999 and 2009 were retrospectively reviewed. A total of 172 cases with a follow-up visit period of 1 year and more were eligible. The children were classified into three groups according to the treatment protocol: ganciclovir treatment (n=49), acyclovir treatment (n=72) and symptomatic treatment (control; n=51). The children in the ganciclovir group received an intravenous drip of 10 mg/kg per day of ganciclovir, administered in twice-daily doses; Seven days later the drip volume was changed to 5 mg/kg, administered once each day; the total course lasting 10-14 days. The children in the acyclovir group received acyclovir orally at 20 mg/kg per day, administered in three times daily doses; the total course lasting 10-14 days. The children in the control group received symptomatic treatment only. In the three groups, indicators including fever course, improvement of isthmitis symptoms, lymph node retraction, hepatic and splenic lymph node retraction time, atypical lymphocyte fallback time and alteration of granulocyte amount after drug use were observed. The long-term follow-up visits covered such indicators as blood routine reexamination, hepatic function, liver and spleen B-ultrasonography, recovery rate, recurrence rate and mortality rate. RESULTS: In the acute phase, there were no differences in terms of fever course, isthmitis improvement, hepatic and splenic lymph node retraction time and the time of atypical lymphocyte falling back to below 10% among the three groups (P>0.05). During the period of follow-up visits between 1 year and 8 years and 10 months, no significant differences were observed in the recovery rate, the recurrence rate and the mortality rate among the three groups (P>0.05). CONCLUSIONS: The efficacies of antiviral therapy for IM children appear to be similar to non-antiviral therapy, suggesting that antiviral therapy fails to be beneficial for IM children.