Thirty-three Tunisian patients, homozygous for Hb S, were examined. Haplotyping using nine restriction sites in theβ-globin gene cluster revealed that the most common type is the Benin type [- - - - + - + - +] which occurs at a frequency of 0.94% (31 cases); only one patient was homozygous for an atypical haplotype which shows some differences with the Benin haplotype at sites 1, 5, 6, and 8 [+-—- + + + +]; the two remaining patients were assumed to be double heterozygotes for the Benin and atypical haplotypes. The presence of the atypical haplotype suggested a double origin of the Bsgene in Tunisia. Moreover, a heterogeneity in the Hb F production was observed, ranging between 2 to 16%, whereas theGγ-globin expression was remarkably homogeneous in our patients with a normal amount approaching 40%. These results suggested the presence of a combination of several control factors.