ABSTRACT The syn-anti conformational equilibrium for a series of nine cyclic nucleotides was studied at semiempirical AM1 level. The AM1 results indicate that for guanosine cyclic 3',5'-monophosphate and their derivatives substituted at 8-position, the syn-conformers are more stable than the anti ones. For purine derivatives without an amino group at position 2, which participate in a hydrogen bonding with the axial oxygen of the phosphate group, the anti conformation is preferred.	 	The AM1 results suggest that syn-anti equilibruim is a dominant factor for the binding of cyclic nucleotides to cyclic phosphodiesterases. Reinterpretation of experimental results for the competitive inhibition of c-GMP-stimulated phosphodiesterase was performed.