Insoluble complexes of adenine nucleotides (AMP, dAMP, ATP, and dATP) and polyuridylic acid as well as guanine nucleotides (GMP, dGMP, and GTP) and polycytidylic acid are formed reversibly when the concentrations of the polynucleotides and especially of the nucleotides are sufficiently high and the temperature is sufficiently low. At moderate concentration of the interactants (0.01-0.02 M), Mg2+ ion is usually required for the interaction. These insoluble complexes have a definite stoichiometry, generally 2U to 1A or 1C to 1G and, in one case, 2C to 1G was found. The base-pairing specificity is the same as that of the polynucleotide interactions. On the other hand, a soluble complex between the mononucleotides and their complementary polynucleotides cannot be detected by optical rotatory dispersion, sedimentation, and viscosity, techniques which were employed successfully before to characterize the adenosine-(U)n system. These data indicate that interaction in these mixtures only takes place when accompanied by a phase transition, such as precipitation or gelation. The following mechanism is proposed. When the conditions are sufficiently favorable, the monomer-polymer interaction occurs through hydrogen bonding between the base pairs and through the cooperative stacking of the mononucleotides along side the complementary polynucleotides. In the complex, mononucleotides become polymerlike. Thus, a phase transition occurs, since the polymer-polymer complexes are insoluble under these conditions. This transition of physical state provides the additional driving force needed for the interaction to proceed by removing the complex into another phase of the system. © 1968, American Chemical Society. All rights reserved.