Dendritic cell (DC) vaccination is an attractive approach to the treatment of patients with lymphoid tumors. To evaluate its feasibility, we have tested the functional properties of DC and T-lymphocytes in patients with treated and untreated chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). Healthy volunteers were used both as controls and as a source of cells for allogeneic mixed leukocyte reaction (MLR). In these reactions, dendritic cells from both untreated and treated patients were comparable to dendritic cells from healthy volunteers. In all the untreated patients studied, autologous dendritic cells promoted the survival and proliferation of both CD4 and CD8 lymphocytes (though the proliferation response was much better in the CD4 subset), whereas only 3 out of 5 treated patients were able to mount this response with CD4 lymphocytes and 4 out of 5 with CD8 lymphocytes. In 3 out of 5 untreated patients, pulsing of DCs with tetanus toxoid promoted a better CD4 response than was achieved with unpulsed DCs, while none of 5 treated patients had an additional response after pulsing with tetanus toxoid. None of patients studied, either treated or untreated, had a better CD8 response to pulsed DCs than to unpulsed ones. During CD4 lymphocyte proliferation, more CD4(+)CD25(hi) lymphocytes were generated in both treated and untreated patients than in healthy controls. Poor proliferation of cytotoxic cells and preferential proliferation of CD4(+)CD25(hi) T-regulatory cells in response to self and/or foreign antigens might be one of the mechanisms responsible for immunosuppression and impaired tumor surveillance in patients with lymphoid malignancies.