We have cloned cDNAs representing five full-length human phosphodiesterase (PDE) 8A splice variants (PDE8As 1-5) from testis and T cells. PDE8A1 encodes a hydrophilic protein of 829 amino acids, containing an N-terminal REC domain, a PAS domain, and a C-terminal catalytic domain. PDE8A2 encodes a protein of 783 amino acids, identical to PDE8A1 but lacking the PAS domain. PDE8A3 encodes a shorter protein equivalent to the C-terminal 449 amino acids of PDE8A1, containing the catalytic but not the REC and PAS domains. PDE8A4 and PDE8A5, though different from each other at the nucleotide level, encode an identical protein equivalent to the C-terminal 582 amino acids of PDE8A1, including half of the PAS domain. The PDE8A gene is revealed to contain 23 exons, and its exon-intron boundaries have been defined. In addition, we have mapped a common transcription initiation site, and further determined the upstream 5'-flanking sequence of 1740 bp containing the putative promoter. Compared to PDE8A1, PDE8As 2-5 appear to be expressed in much lower abundance. Among various tissues and organs, PDE8A1 and PDE8A2 are expressed at various levels.