The DNA tetramer d(CpGpCpG) or CGCG crystallizes from high-salt solution as a left-handed double helix, the Z' helix. Its structure differs from that of the other known left-handed helix, Z-DNA, by a Cl'-exo sugar pucker at deoxyguanosines rather than C3'-endo, and these represent two alternative solutions to the same steric constraint arising from the syn glycosyl bond orientation. The apparent molecular basis for the Z to Z' transition in going from intermediate to high salt is substitution of a bound anion for water at guanine amino groups, and consequent charge repulsion of anions and backbone phosphates.