All cases of Cytomegalvirus-related disease in previously healthy immunocompetent subjects admitted to the University Hospital of Catania between 1990 and 2000 were reviewed. Eighty-one immunocompetent subjects were discharged with a diagnosis of acute cytomegalic disease. Nevertheless, only in 26 cases was the diagnosis confirmed by the determination of the specific immunoglobulin M, viremia or antigenemia. Fifteen subjects presented with a mononucleosis-like syndrome. Eleven subjects had a more severe form of the disease with organ involvement: 3 hepatitis, 3 interstitial pneumonia, 2 aseptic meningitis, 2 ulcerative colitis and 1 peripheral vasculitis. All patients recovered. Two out of 11 severe cases were treated with ganciclovir and 7 with steroids; the remainder received only supportive treatment. Large-scale surveys are required to assess the real impact of Cytomegalovirus disease in immunocompetent subjects and to elaborate guidelines for the management of severe cases.