Standard free-energy changes for reactions involving single- and double-stranded nucleic acids have been related to that for polynucleotide synthesis from ribonucleoside diphosphates for which deltaG degrees' approximately O. For polynucleotide formation from triphosphates this quantity is about -1 kcal. In the replication reaction the base pairing interactions are quantitatively of comparable importance. Production of a hydrolytic break in a double strand is substantially less favorable than in a single strand. The resealing of breaks utilizing ATP and NAD+ have similar free-energy changes and are entropy driven processes. The highly exergonic hydrolysis of pyrophosphate is maintained to be of significance for both in vivo and in vitro polymerizations.