In order to determine the factors responsible for the differentiation of cytomegalovirus (CMV) hepatitis and Epstein-Barr virus (EBV) hepatitis, the clinical features and laboratory data of both types of hepatitis were retrospectively analyzed in 20 patients with CMV and 11 patients with EBV. While most signs and symptoms of CMV and EBV hepatitis showed no significant differences, we found that cervical lymph- adenopathy was more common in EBV hepatitis than in CMV hepatitis (p < 0.01). Frequency of epigastralgia was more common in CMV hepatitis than EBV hepatitis (p < 0.05). The percentage of peripheral blood monocytes in the white blood cell count in CMV hepatitis was greater than in EBV hepatitis (p < 0.01). Low CD4 levels and high CD8 levels made CD4/CD8 low in peripheral lymphocytes of both groups of hepatitis. Ten EBV hepatitis patients received antibiotics in the early stage of the disease in which two (25%) developed severe erythematous rashes. Four CMV hepatitis patients received antibiotics and did not develop rashes. Identification of early clinical parameters capable of differentiating CMV hepatitis from EBV hepatitis is important.