A number of recent studies have shown that simple repetitive d(CA/TG) dinucleotide sequences adopt a left-handed non-B-DNA structure under negative superhelical stress. The pattern of chemical reactivities and the helical parameters observed for these sequences differ significantly from those of standard Z-DNA. In this study, the data for two naturally occurring d(CA/TG)n sequences are reevaluated by a statistical mechanics treatment of the B- to Z-DNA transition. The behavior of these sequences under negative superhelical stress is accurately simulated by this model, including the multiple and discrete transitions observed for the rat prolactin promoter. Furthermore, the average helical twist for the left-handed structure of d(CA/TG)n deviates < 2% from that expected for standard Z-DNA. Finally, the predicted distribution of the junctions between B- and Z-DNA are shown to account for differences observed in the patterns of chemical reactivity of d(CA/TG)n and d(CG)n. Thus, no new left-handed structure that differs from Z-DNA is needed to describe the supercoil-induced conformation in d(CA/TG)n sequences.