The human B-lymphoma cell lines BJAB and Daudi, as well as the human pre-B cell line KM3, were found to down-regulate steady-state immunoglobulin RNA levels 2- to 4-fold after stimulation with phorbol 12-myristate-13-acetate (PMA) for 24 hr. No down-regulation of the transcriptional rate of a kappa promoter could be observed in any of these cell lines upon transient expression transfection. The observed down-regulation of steady-state immunoglobulin RNA affected both the secretory and the membrane form of the mu transcript equally. When freshly isolated chronic lymphocytic leukemia (CLL) cells where tested for their response to PMA, three of four isolates responded by down-regulating their steady-state immunoglobulin RNA levels.