Phospholipase C (PLC)-gamma 1 and -gamma 2 play a pivotal role in signal transduction for cell proliferation and differentiation. The enzyme activity and protein level of PLC-gamma 1 were markedly decreased in the human histiocytic leukemia U937 cell line during the differentiation process which is induced by phorbol 12-myristate 13-acetate (PMA) but those of PLC-gamma 2 were not altered. Northern blot analysis showed that the levels of PLC-gamma 1 and -gamma 2 transcripts were not changed. These results suggest that the expression of PLC-gamma 1 during the PMA-induced differentiation may be down-regulated by post-transcriptional processing.