The involvement of cAMP- and cGMP-dependent signal systems into the regulation of the contractile reaction of smooth muscles of the rabbit pulmonary arteries was studied using a mechanographic method. For modulation of intracellular level of cyclic nucleotides we used adenylate cyclase activators beta-adrenoceptor agonist isadrin, guanylate cyclase inhibitor methylene blue, penetrating analog dibutyryl-cAMP, and phosphodiesterase inhibitors. The mechanisms of cAMP- and cGMP-dependent regulation of smooth muscle contractile activity were realized in close interrelationship, and the key component of this was cyclic nucleotide phosphodiesterases. The ratio of activities of phosphodiesterase subtypes in smooth-muscle cells can essentially modulate the adrenergic effects in the pulmonary artery wall and even invert them.