Differentiation of B lymphocytes into plasma cells is regulated by the interaction of distinct transcription factors (TFs) which activate gene expression in a lineage- and stage-specific pattern. Using reverse transcription polymerase chain reaction, we studied the expression of five TFs (octamer binding factor oct-2, ets family members PU.1 and Spi-B, pax gene family member BSAP, and Blimp-1) in (1) human cell lines with a plasma cell phenotype, (2) primary malignant plasma cells [obtained from patients with plasma cell leukaemia (PCL) and multiple myeloma], and (3) normal human plasma cells generated in vitro or isolated from normal bone marrows. The expression pattern was compared with TFs expressed by normal CD19+ B lymphocytes and by B cells from chronic lymphocytic leukaemia patients. Our results showed that plasma cells expressed a restricted set of TFs compared with CD19+ B lymphocytes, with continued expression of Spi-B and oct-2, increased Blimp-1 expression, and downregulation of BSAP and PU.1. Cells from PCL lost Spi-B and PU.1 expression completely and expressed only oct-2 and Blimp-1, and thus resembled plasma cell lines. Human plasma cell differentiation therefore seems to be positively regulated by Blimp-1; whether this TF has any oncogenic potential will have to be analysed in future studies.