Abstract: Cytosolic extracts from a human lymphoblastoid B cell line, RPMI 8392, established from a patient with acute lymphocytic leukemia, contain two major forms of cyclic nucleotide phosphodiesterase (PDE): Ca.sup.2+ --calmodulin dependent PDE (PDE1) and cAMP specific PDE4 subtypes. In contrast, normal quiescent human peripheral blood lymphocytes (HPBL) are devoid of PDE1 activity. Using reverse transcription-polymerase chain reaction (RT-PCR), the mRNA encoding the 63 kDa form of PDE1 (PDE1B1) is expressed in RPMI 8392 cells, but not in normal, resting HPBL. This mRNA is, however, induced in HPBL following mitogenic stimulation by phytohemagglutinin (PHA). Also using RT-PCR, the full open reading frame for human PDE1B1 cDNA was cloned from RPMI 8392 cells and it encodes a protein of 536 amino acids with 96% identity to bovine, rat and mouse species. RT-PCR also identifies the presence of PDE1B1 in other human lymphoblastoid and leukemic cell lines.