Fifty seven Egyptian children aged 1.5 to 9.5 years with mild splenomegaly (less than 3 cm below the costal margin) were screened for antibodies against the three common viruses of the Herpes group: Cytomegalovirus (CMV), Epstein-Barr (EB) and Herpes type 1 virus. A group of 57 healthy children were studied similarly. All patients were subjected to a comprehensive laboratory and clinical work up to exclude any hematological, metabolic or malignant etiology for the splenomegaly. Splenic aspirates from five cases were examined histologically and by immunohistochemistry for the antigens of CMV. Only primary or reactivation of CMV might be considered a cause of splenomegaly, as there was a statistically significant increase in the prevalence of IgM antibodies to CMV in the patients compared to normal controls (63% of patients and 19.4% of controls had IgM antibodies, P less than 0.001; 68.3% of patients and 54% of controls had IgG antibodies, P is insignificant). An almost equal proportion of children with and without splenomegaly had antibodies to EB-Viral Capsid Antigen (EBVCA) both IgG and IgM. (28% of cases and 33% of controls had IgM antibodies; 26% of patients and 21% of controls had IgG antibodies). A role of Epstein-Barr viral infection could not be ruled out in these patients. There was a higher prevalence of antibodies to Herpes type 1 virus in asymptomatic controls than in children with splenomegaly. (10% of patients and 43% of controls had IgM antibodies, 10.6% of patients and 38% of controls had IgG antibodies).