1 The relaxant properties of the type IV adenosine 3',5'-cyclic monophosphate phosphodiesterase (cyclic AMP PDE) inhibitor, rolipram and the P2-selective and non-selective P-adrenoceptor agonists salbutamol and isoprenaline, were compared on the guinea-pig, bovine, and mouse trachea and porcine bronchus all precontracted with methacholine (EC30).2 Rolipram and both P-agonists produced concentration-dependent reversal of the methacholineinduced tone in the four airway preparations.3 Isoprenaline and salbutamol were similar in potency on the guinea-pig 8.06) and bovine (-loglo IC50:8.52, 8.40) airways. In contrast, salbutamol was much less potent than isoprenaline on the mouse trachea (>1000 fold) and the porcine bronchus (>100 000 fold). 4 The potency of rolipram approached that of isoprenaline on the guinea-pig and bovine trachea (132-adrenoceptors predominate). However, rolipram was significantly less active than isoprenaline on the porcine bronchus (1000 fold) and mouse trachea (>2000 fold) where P2-adrenoceptors predominate.5 Siguazodan, the type III cyclic AMP PDE inhibitor, produced concentration-dependent relaxations of the porcine bronchus and guinea-pig trachea contracted with methacholine. Siquazodan was 100 fold more active than rolipram in pig tissues indicating the type III isoenzyme may be of greater functional significance in this tissue. In contrast, siguazodan was 15 times less potent that rolipram in guinea-pig airways suggesting a greater role for the type IV PDE.6 These findings may reflect a possible relationship between the P2-adrenoceptor subtype and the functional importance of the type IV PDE isoenzyme. A similar relationship may exist between P,-adrenoceptors and the PDE type III isoenzyme.