Two patients affected by severe hypogammaglobulinemia classified as CVI were studied. Both patients showed an increase in peripheral T cells and a normal or elevated number of surface immunoglobulin-bearing cells (sIg+); the T cell subsets showed a decrease of CD4 and an increment of CD8 cells with an inversion of the CD4/CD8 ratio. Patient peripheral blood mononuclear cells (PBMC) did not proliferate after Staphylococcus aureus Cowan I (SAC) activation. Moreover, patient PBMC were not able to differentiate into plaque - forming cells (PFC) either spontaneously or after pokeweed mitogen (PWM) stimulation. The immunoglobulin synthesis from patient PBMC stimulated in vitro by PWM was very little as compared to controls. When isolated patient B cells were cultured in the presence of exogenous B cell growth factor (BCGF) and BCGF plus anti-mu and anti-delta antibodies, no proliferation was observed. Taken together the results concerning B cell function of our CVI patients indicate the presence of an intrinsic defect of B cells. These cells are normal in number, but they are not able to leave the resting state, enter the activation state, proliferate and differentiate into Ig secreting cells. Moreover the alteration of the T cell subset proportions seems to suggest an impaired cooperation between B and T cells.