The cDNA encoding rat cGMP-binding, cGMP-specific phosphodiesterase (cGB-PDE) was isolated from a rat lung cDNA library. Although the deduced amino acid sequence showed 93.4% similarity with that of bovine cGB-PDE, the N-terminal portion of rat cGB-PDE was extremely different from that of bovine. Northern blot analysis indicated that cGB-PDE transcripts in rats were expressed not only in aorta and lung, but also in several other tissues including cerebellum. In situ hybridization analysis demonstrated that cerebellar expression of cGB-PDE was confined to Purkinje cell layers in adult rats. To clarify the role of cGB-PDE in the cerebellum, we investigated expression of cGB-PDE mRNA in rats of various ages. cGB-PDE mRNA was not observed in the cerebellum of newborn rats, but levels of a cGB-PDE mRNA were markedly increased between 4 days and 28 days of age and reached a maximum in eight-week-old rats. In this study, we suggest that cGB-PDE plays important roles not only in regulating the relaxation of vascular vessels, but also in establishing neuronal networks in the cerebellum at an early postnatal stage. In addition the NO/cGMP/cGB-PDE pathway appears to be essential for the induction of long-term depression.