A 57-year-old man with a history of recurrent infections from the age of 50 was hospitalized with a diagnosis of common variable hypogammaglobulinemia (CVH). Immunological studies revealed a severe reduction of circulating immunoglobulins of all classes. Immunophenotyping of peripheral blood mononuclear cells (PBMC) with monoclonal antibodies, revealed normal values of total B and T cells with CD4/CD8 ratio sharply reduced (0.35) as compared to normal (1.6) because of an increase of CD8 and a decrease of CD4 cells. The surface expression of IL-2 receptor was normal. Natural cytotoxic and phagocytic system presented several abnormalities: a deep impairment of NK activity was found in spite of a normal number of NK cells, as ascertained by Leu 19 and B73.1 monoclonal antibodies. The defective NK activity was not restored by interferon alfa, but was normalized by recombinant IL-2. Phagocytic function, as defined by zymosan-stimulated O2- production was almost absent. The involvement of natural cytotoxic and phagocytic systems in CVH has been rarely reported; the possible causative role of a chronic viral infection (Epstein-Barr virus?) is discussed, on the base of anamnesis.