We investigated the immunological mechanism of the low level of circulating immunoglobulin and depressed primary and secondary responses of patients with chronic lymphocytic leukaemia (B-CLL) using purified non-leukaemic B cells in vitro. To assess the function of the non-leukaemic B cells we separated them from the much larger leukaemic population, which expresses the pan-T cell marker CD5, by immunoabsorption using anti-CD5 antibodies and Dynabeads. Immunoglobulin production was measured after the cells had been cultured with the B cell mitogens, pokeweed mitogen (PWM) and Staphylococcus aureus Cowan strain 1 (SAC). Autologous T cells that were found to function normally in our systems were added to cultures containing PWM. Non-leukaemic B cells from 15 B-CLL patients produced 539 ng/ml, immunoglobulin (mean value) with SAC and 162 ng/ml with PWM compared with 14,182 and 5513 ng/ml, respectively, from B cells from normal, age-matched control patients. Most of the immunoglobulin produced in the non-leukaemic B cell cultures carried the light chain associated with the leukaemic clone. We conclude that even at early stages in the disease (12 patients were Rai stage 0 patients) when the total serum immunoglobulin levels are still near normal, the B cells respond poorly to B cell mitogens.