Phosphodiesterases (PDEs) are enzymes that maintain the integrity of various cyclic nucleotide signaling pathways by regulating the cellular levels of cyclic nucleotide secondary messengers. PDE-6 is the only member of the phosphodiesterase family that is known to be regulated by a G-protein. The gamma-inhibitory subunit of PDE-6 facilitates the interaction between G-protein (transducin) and PDE-6 and PDEgamma is the only known molecule via which G-protein and phosphodiesterase interact. We have found the expression of PDEgamma-like transcripts and proteins in non-retinal tissues such as testis and lungs by both RT-PCR and Western blotting. We identified two main isoforms of PDEgamma, which we name rod PDEgamma and cone PDEgamma. The cone PDEgamma undergoes splicing to give rise to a short isoform, which has a truncated C-terminal. We have also shown that p14 is a mixture of rod and cone gamma, while p18 corresponds to the phosphorylated rod gamma. Our results are suggestive of a widespread physiological interaction between G-protein and phosphodiesterases.