To determine the prevalence of the sickle cell gene (betaS) in Yemen and amongst people from different regions of the country living in the capital, Sana'a City, cord blood samples from 1,500 consenting mothers were collected from hospitals in Sana'a City between July and December 2001. The names and original homes of the parents were recorded. Cation exchange high performance liquid chromatography (HPLC) analysis was used for screening, while isoelectric focusing (IEF) and DNA polymerase chain reaction (PCR) were used to confirm Hb S [beta6(A3)Glu-->Val]. Thirty-three samples were found to show Hb FAS, giving an overall likely betaS gene frequency of 0.011. The betaS gene frequency varied with the part of the country from which the parents came. Amongst people from Taiz and Haja in the west, the gene frequency was more than 0.04, but less than 0.004 amongst people from Ibb, adjacent to the governorate (administrative division) of Taiz. Of 66 chromosomes from babies carrying the betaS gene, only 1.5% also carried the -158 (C-->T) Ggamma-globin gene XmnI site compared with 16.1% of 168 chromosomes from babies without the betaS gene from the same regions. The results of this study show a higher betaS gene frequency in the western coastal part of Yemen than in the central mountainous and eastern desert areas. The incidence of affected homozygous births may therefore reach 20/10,000 in certain areas, although it is much lower than this overall. Limited health resources can best be invested in developing a program of education, screening and health care, initially prioritizing those communities residing in the western areas of Yemen with the highest betaS gene frequency.