A probe representing the Drosophila dunce+ (dnc+) gene, the structural gene for a cAMP phosphodiesterase (PDEase), detects homologous sequences in many different organisms, including mouse, rat, and human. Genomic and cDNA clones representing a homolog of the Drosophila dnc+ gene were isolated from rat libraries and characterized. This gene has been named ratdnc-1. One cDNA clone defines a large open reading frame of approximately 1.8 kilobases (kb), predicting a protein sequence of 610 amino acids with significant homology to a conserved domain of approximately 275 residues found in most other PDEases. The amino acid identity value to the Drosophila cAMP PDEase within this domain is a striking 75%. Other cDNA clones show blocks of sequence divergence from this cDNA clone close to the predicted N terminus, indicating the potential existence of a family of related enzymes encoded by alternatively spliced messenger RNAs from ratdnc-1. Genomic blotting experiments suggest the existence of at least one other rat gene with homology to ratdnc-1. RNAs homologous to ratdnc-1 are heterogeneous in size between tissues, with heart containing a major transcript of 4.4 kb and brain one of 4.0 kb. The potential identity of the product of the ratdnc-1 gene with known PDEases is discussed.