The effect of therapeutic irradiation upon B lymphocyte function was investigated in patients with various malignancies. The test system used was a reverse hemolytic plaque assay, which made it possible to study the activation and differentiation of B lymphocytes into immunoglobulin-secreting cells (ISC). Peripheral blood lymphocytes from normal individuals and patients before and after radiotherapy were stimulated in vitro with the polyclonal B cell activator pokeweed mitogen, and the number of ISC was estimated. B cell reactivity was markedly reduced in those patients who had received irradiation within the last six months. In patients in whom radiotherapy had been terminated more than 12 months before the lymphocytes were tested, B cell reactivity was comparable to that of patients prior to radiotherapy. By means of marker analyses, there was a reduction of B lymphocytes and T lymphocytes in the peripheral blood with a preponderance of T helper cells. Several mechanisms--e.g., reduced or defective B cell differentiation, altered regulatory T-helper or suppressor cell function or activation of suppressive monocytes--could be responsible for impaired B cell reactivity after radiotherapy.