Proton magnetic resonance spectra of 30 adenine nucleosides have been obtained in dilute (0.001 to 0.05 M) aqueous or dimethyl sulfoxide solutions and have been analysed with respect to structuredependent variations of the purine proton chemical shifts. In 2Hz0 the resonance signal of H-8 shows a marked dependence upon the nature of substituents linked to C-4' of adenine ribofuranoside derivatives and upon the presence of a 2': 3'-O-isopropylidene group while H-2 is relatively unaffected.Therefore the chemical shift difference, 6H-8 -6H-2 = Ad, may serve as an indicator of intramolecular ribose-base interact ons. d6 varies with the chemical nature of C-4' or C-5' substituents in the order: ammonium, sulfonium (0 ppm) < hydrogen < hydroxyl amino < thio < halogen < phosphate, carboxylate (0.4 ppm), and decreases with increasing chain length of these substituents. These results suggest the existence of electrostatic and dipolar repulsion or, in the majority of cases, attractive forces between the C-5' and C8-H regions of adenine nucleosides which have been previously demonstrated for 5'-nucleotides only. They imply a strong preference of most adenosine derivatives with unsubstituted 2' and 3'-hydroxyl groups for the anti-conformation range and the gauche, gauche C-5' conformation. In dimethyl sulfoxide, basically the same situation exists but different substituents exhibit smaller individual A6 variations than in water, indicating different solvation shells. In this solvent two additional conformation-stabilizing contributions can be recognized, viz. an interaction of the bridge oxygen (0-4') of ribose with adenine, and a hydrogen bond between H-8 and a 5'-carboxylate anion. This energetic stabilisation of the anti and g,g-conformers by most types of adenosine C-5' substituents supports the "rigidity" concept of nucleotides, extending it to the nucleoside level. The only exception found is 5'-nitromethyladenosine in which ultraviolet, circular dichroism and magnetic resonance spectra suggest rotation of the adenine base to a "non-classical" conformation due to base-chain n-electron interaction. The anti-conformation of the adenosine derivatives used in this study can in some cases be correlated with their enzymatic deamination by adenosine and AMP aminohydrolase.The biochemical function of nucleosides and nucleotides as substrates or effectors of the degrading and polymerizing enzymes of nucleic acid metabolism depends critically upon the molecular conformation which they assume in solution. The three substructures of a typical nucleoside, viz. the heterocyclic base, the pentofuranose ring and the exocyclic 5'-carbon atom carrying various substituents, are known to be arranged in certain relative orientations which have been Part 1 of a series entitled Forces Stabilizing the Conformation of Nucleosides in Solution.