The beta-globin gene cluster has shown high polymorphic diversity organized in 5' and 3' haplotypes (Hps). beta(S)-Chromosomes are in linkage disequilibrium with the 5' Hps Bantu, Benin, Senegal, Cameroon, and Arab-Indian. In Mexican mestizos with African west coast origins, we observed the following 5' Hps in beta(S)-chromosomes: Bantu, 78.8%; Benin, 18.2%; and atypical Hp 9, 3.0%. With the purpose of establishing the 3' Hps, we analyzed 35 polymorphic sites--6 by RFLP analysis and 29 by DNA sequencing--in 33 unrelated beta(S)-chromosomes. The polymorphic sites were structured according to Harding et al. [R.M. Harding, S.M. Fullerton, R.C. Griffiths, J.B. Clegg, Archaic African and Asian lineages in the genetic ancestry of modern humans, Am. J. Hum. Genet. 60 (1997) 772-789] and Lapoumeroulie et al. [C. Lapoumeroulie, O. Dunda, R. Ducrocq, G. Trabuchet, M. Mony-Lobe, J.M. Bodo, P. Carnevale, D. Labie, J. Elion, R. Krishnamoorthy, A novel sickle cell mutation of yet another origin in Africa: the Cameroon type, Hum. Genet. 89 (1992) 333-337]. All Bantu beta(S)-chromosomes showed the 12A1 3' Hp with (AT)6T9 repeats (84.9%), a novel 3' Hp. The Benin Hp was 2B2, with (AT)8T4 (12.1%), and the atypical Hp 9 4B1, (AT)8T5 (3.0%). Because of the high linkage disequilibrium observed for the Bantu and 12A1 Hps, we expect that, if there is a single origin of the Bantu beta(S) mutation, all must show the 12A1 polymorphic DNA sequence in the 3' Hp. A correlation between the 5' and 3' Hps could be observed with the other beta(S) mutations. The atypical Hp 9 was also atypical at the 3' Hp, with the same repeats as observed with the Cameroon beta(S) mutation; however, it differed in one position from the typical Lapoumeroulie Cameroon Hp, indicating that these beta(S)-chromosomes arose by different genetic mechanisms or by a novel beta(S) mutation. We stress the importance of the study of DNA polymorphisms at 3' Hp to allow understanding of the genetic diversity of beta(S)-chromosomes, as well as their implications in beta(S) gene expression and the possible effects on the clinical phenotype.