Phosphodiesterases (PDE) enzymatically convert the cyclic nucleotide second messengers cAMP and cGMP to 5’-AMP and 5’-GMP, respectively, thus terminating signal transduction. The cAMP-specific PDE4 isoforms may be particularly important in certain respiratory and neurological diseases. CP 80,633 is a selective inhibitor of PDE4 (IC50 = 1.27 μM for PDE4 versus. >100 μM for PDE1, PDE2, PDE3, and PDE5). It potentiates PGE1-dependent increases in cAMP levels in eosinophils, monocytes, and T-cells, inhibits eosinophil superoxide production (IC50 < 0.6 μM), and blocks LPS-induced TNF-α release from monocytes (IC50 = 0.22 μM). CP 80,633 (1 mg/kg) significantly reduces antigen-induced airway inflammation in atopic guinea pigs, monkeys, and mice.