In the present study, we show that UT7D1 cells, derived from the pluripotent cell line UT7, express high levels of histidine decarboxylase (HDC) mRNA spontaneously. These cells conserve the ability to differentiate into megakaryocytes upon stimulation with PMA, while greatly increasing their HDC activity. We provide evidence that enhanced HDC activity reflects the basophil rather than the megakaryocytic differentiation potential of UT7DI cells. Indeed, in addition to HDC mRNA, they express spontaneously several other mRNA coding for molecules present in basophils (FcepsilonRI, CCR3, IL-4Ralpha, IL-5Ralpha). Furthermore, the basophil antigen Bsp-1 is displayed on the surface of some UT7D1 cells in response to PMA concomitantly with increased histamine synthesis and mRNA expression of typical basophil-derived cytokines (IL-6, IL-4, and IL-13). Nevertheless, PMA cannot sustain the differentiation of this lineage, because mRNAs for basophil markers gradually diminish during long-term culture, whereas molecules associated with the megakaryocytic lineage remain prominent. In support of the notion that HDC activity is not related with megakaryopoiesis, we show that PMA-induced CD41 expression and PDGF transcription occurs in the K562 cells, though neither HDC mRNA nor any known basophil marker are expressed in these conditions. In contrast, all these markers are expressed in the basophilic leukemia cell line KU812F. Interestingly, the megakaryocytic cell line HEL produces also substantial amounts of histamine and expresses FcepsilonRI, thus revealing its basophil differentiation potential. HEL as well as KU812F need not be stimulated with PMA to react with Bsp-1 mAb, suggesting that they are more engaged into the basophil differentiation scheme than UT7D1. Other leukemic cell lines unrelated to the megakaryocyte or basophil lineage, like HL60 and U937 do neither synthesize histamine nor express basophil markers before or after PMA stimulation. To our knowledge, this is the first evidence for a factor-dependent cell line with megakaryocyte/basophil bipotentiality with which early stages of basophil commitment can be analyzed.