Within the first year after T cell depleted bone marrow transplantation, co-cultures of T cells and non-T cells from 32 individual recipients examined on 43 occasions generally failed to produce increased quantities of immunoglobulin in response to stimulation with pokeweed mitogen or B cell differentiation factors. Failure occurred even in the presence of significant numbers of CD20 + ve B cells. The non-production of Ig appears to be due to a functional B cell defect, since adding marrow donor (syngeneic) T cells to recipient B cells in the presence of PWM or conditioned medium did not lead to immunoglobulin production. This B cell deficit persisted for 1 year. In contrast helper activity in the recipient T cell enriched population returns rapidly and by 6 weeks after transplant co-cultures of marrow donor B cells and recipient T cells produce comparable amounts of Ig to co-cultures of donor T and B cells. This prolonged defect of B cell function in vitro correlates with a year long delay before humoral responses to novel vaccine antigens can be elicited in vivo.