Treatment with rituximab, either alone or in combination with antiblastic drugs, causes significant depletion of circulating B-lymphocytes and modifications of B cell maturation in the bone marrow. In the present study, we analyzed the kinetics of hematogones in bone marrow samples from 55 patients suffering from non-Hodgkin lymphomas and treated with rituximab-containing regimens. Maturation arrest at the level of stage 2 hematogones, along with complete depletion of naïve, mature B-lymphocytes, was observed as short-term effects (2 months after completion of chemo-immunotherapy). Further bone marrow samples, obtained 12 months after the last rituximab infusion in 21 patients undergoing long-term follow-up and treated with rituximab maintenance therapy, showed complete normalization of B-lymphocyte ontogeny. Hypogammaglobulinemia developed in 26 patients, and was still observed in nine of the 21 patients undergoing long-term follow-up. Our study provides novel data on hematogone kinetics in the setting of patients with non-Hodgkin lymphomas treated with chemo-immunotherapy containing rituximab and with rituximab maintenance. Our observations show that hypogammaglobulinemia can persist in a significant percentage of patients, despite complete recovery of B-lymphocyte ontogeny.