Abstract: Isolated cDNA clones from human brain (frontal cortex) cDNA libraries that encode a unique subtype of the low K.sub.m, cAMP-specific phosphodiesterases (PDE IVs) are disclosed. Analysis of the distribution of hPDE IV.sub.B mRNA expression in various human tissues using a nonconserved fragment of the cDNA as a probe revealed a restricted pattern of expression, with an .about.4-kb MRNA detected in brain, heart, lung and skeletal muscle and not in placenta, liver, kidney or pancreas. Furthermore, an additional .about.5-kb hPDE IV.sub.B.sup.- related mRNA species was detected in brain tissue. Expression of hPDE IV.sub.B in a genetically-engineered PDE-deficient strain of the yeast Saccharomyces cerevisiae resulted in the overproduction of cAMP PDE activity which displayed the expected kinetic characteristics for a PDE IV: 1) low K.sub.m (4.3 .mu.M) for cAMP, 2) high K.sub.m (>3 mM) for cGMP, and 3) sensitivity to rolipram (K.sub.i =0.085 .mu.M), a selective inhibitor of PDE IV. Recombinant HPDE IV.sub.