Hunter syndrome (mucopolysaccharidosis II) is an X-linked lysosomal storage disorder caused by the deficiency of iduronate sulfatase (IDS), the gene of which is located at Xq28. A relatively high frequency of Hunter disease among Ashkenazi and Moroccan Jews in Israel was observed. Genetic analysis of the patients with Hunter disease in these ethnic groups indicated the absence of new mutations and a two-fold excess of individuals with the mutant allele over non carriers. This unusual phenomenon is unique to these ethnic groups and is suggestive of a prenatal selection process favoring the Hunter allele. Studies of the IDS gene structure and its flanking region are performed with the aim of detecting the mutations causing the disease in these patients and thus develop the most accurate diagnostic procedure for carrier identification among female relatives in these families. Furthermore, these studies are also aimed at identifying the unique molecular structure in the IDS gene or its flanking region which is the basis for the selection process. RFLP analysis using the cDNA gene (pc2S15) and DNA probes closely linked to the IDS gene, as well as the study of CA repeats in a closely linked region, indicated the absence of common haplotypes among Ashkenazi or Moroccan patients, excluding a linkage disequilibrium between a putative advantageous linked gene to the Hunter mutation in our patients. Studies of the IDS gene indicated a partial deletion in two patients while the other 12 patients had an apparent intact gene.(ABSTRACT TRUNCATED AT 250 WORDS)