Two tables have been constructed showing the crystal and solution conformations of short sequences of DNA. Each of these DNAs has been found to be in one of three different conformations-the A, B, or Z form-depending upon the base sequence and the environmental conditions. A set of rules is presented showing the tendency of certain base pairs to direct the DNA conformation into the A, B, or Z genus in saturated salt solutions and in crystals. These rules are based on a consideration of nearest-neighbor interactions that are interpreted in terms of 10 different two-letter code words made from the letters denoting the bases guanine (G), cytosine (C), adenine (A), and thymine (T). One table discusses the effect on DNA conformation of 3 strong words that tend to direct a DNA oligomer into either the A, B, or Z genus in crystals or in aqueous solutions containing a high salt concentration (6 M). The second table discusses the remaining 7 code words that appear to have a much weaker effect on conformation. The sequences that are most likely to lead to A-Z, B-Z, and A-B junctions are discussed, as is the possible biological significance of these rules.The biological activity of DNA is carried out in association with numerous proteins in order to perform various cellular functions. Protein-nucleic acid interactions are often discussed in terms of two main characteristics-the overall topology of the two partners and the interactions between the nucleotides and the main chain or side chains of the protein (1). The primary specificity of the DNA-protein interaction is undoubtedly governed by the base-sequencedependent array of hydrogen-bonding donor and acceptor patterns that occur along the major and minor grooves of the DNA double helix (2-4). However, it is reasonable to assume that variations in the conformation of DNA may occur along the double-helical axis as it performs its functions in the cell and that these variations in conformation may play a role in the regulation of its biological function. Although the usual conformation of DNA is the canonical B form, it may be that, through interaction with other components in the cell, particularly proteins, partial or total change from this form may occur in regions of DNA. Even a partial change from the canonical B conformation toward the A genus or Z genus would result in a deformation of the hydrogen-bonding donor and acceptor patterns along the major and minor grooves. This effect could be used to aid DNA-binding proteins in locating base-sequence-specific binding sites. As we will show, the possible conformational variations of DNA appear to be determined by specific base sequences as well as the environment.