Fluorescence in-situ hybridization (FISH) has been used to study the spatial orientation of subtelomeric chromosome regions in the interphase nucleus. Compared to interstitial chromosomal sites, subtelomeres showed an increased number of somatic pairings. However, pairing frequency also depended on the specific regions involved and varied both between different subtelomeres and between different interstitial regions. An increased incidence of somatic pairing may play at least some role in the frequent involvement of the subtelomeres in cytogenetically cryptic chromosome rearrangements. In patients suffering from facioscapulohumeral muscular dystrophy (FSHD), which is associated with a deletion of subtelomeric repeats, the FSHD region on 4qter showed a changed pairing behavior, which could be indicative of a position effect and/or trans-sensing effect as a cause for disease.