A total of seven DNA bend sites were mapped in the 4.4-kilobase human beta-globin gene region by the circular permutation assay. The periodicity of these sites (except one) was about every 700 (average 685.5 +/- 267.7) base pairs. All of the sites contained the sequence feature of short poly(dA) tracts, which are typical of DNA bending. The relative positions of the sites to the cap site were identical to those in the epsilon-globin gene region, suggesting that the bend sites were conserved during molecular evolution of the two globin genes. To explain this periodicity and conservation of the sites within the evolutionary unstable noncoding regions, we focused upon the appearance of a potential bend core sequence, A2N8A2N8A2 (A/A/A), and its complement, T2N8T2N8T2 (T/T/T). These sequences appeared in or very close to most of the bend sites of the globin gene regions, whereas other A+T-rich sequences or candidates for DNA bending did not. The distances between any two of the core sequences in the entire beta-globin locus showed a strong bias to a length of about 700 base pairs and its multiples, suggesting that the periodicity exists throughout the locus. The data presented here strengthen the idea of sequence-directed nucleosome phasing.