Several partial cDNA clones encoding cGMP-stimulated PDE were isolated from a Lambda Zap II bovine brain cDNA library, purified and sequenced. Deduced amino acid sequence from one clone exhibited extensive similarity to amino residues 311-921 of a cGMP-stimulated PDE purified from bovine heart and sequenced by Le Trong et al. (Biochemistry 29: 10280, 1990). The sequence of a photolabelled peptide began at residue #432, indicating that at least one non-catalytic cGMP-binding domain was downstream from this residue. Our results further suggest that different cGMPstimulated PDEs may exhibit considerable homology, at least in the cGMP-binding region(s) and catalytic domains.