An empirically based relationship between overall complex stability (-Delta G degrees) and various possible component interactions is developed to probe the question of whether the A center dot T/U and G center dot C base-pairs exhibit enhanced stability relative to similarly hydrogen-bonded complexes. This phenomenological approach suggests ca. 2-2.5 kcal mol(-1) in additional stability for A center dot T owing to a group interaction containing a CH center dot center dot center dot O contact. Pairing geometry and the role of the CH center dot center dot center dot O interaction in the A center dot T base-pair were also probed using MP2/6-31+G(d,p) calculations and a double mutant cycle. The ab initio studies indicated that Hoogsteen geometry is preferred over Watson-Crick geometry in A center dot T by ca. 1 kcal mol(-1). Factors that might contribute to the preference for Hoogsteen geometry are a shorter CH center dot center dot center dot O contact, a favorable alignment of dipoles, and greater distances between secondary repulsive sites. The CH center dot center dot center dot O interaction was also investigated in model complexes of adenine with ketene and isocyanic acid. The ab initio calculations support the result of the phenomenological approach that the A center dot T base-pair does have enhanced stability relative to hydrogen-bonded complexes with just N-H center dot center dot center dot N and N-H center dot center dot center dot O hydrogen bonds.