The fragile X syndrome is recognized as the most common heritable condition resulting in mental retardation. The disabilities are substantial, and therefore early detection is mandatory to assist with reproductive counseling of families in which the fragile X syndrome has occurred. Highly accurate, direct DNA diagnostic testing can now be performed to diagnose the fragile X syndrome without the involvement of individual family members, as was the situation with the use of DNA linkage analysis. Such testing is rapidly becoming a standard diagnostic tool for screening of individuals with suspected fragile X syndrome, of potential unaffected carriers, and of patients with undefined mental retardation. Fragile X testing should be considered for all children with developmental delay of unknown cause. Autistic children will occasionally be found to have mutations in FMR-1. Detection of affected individuals will allow early intervention for these individuals and will assist families with their reproductive decisions (including prevention) in subsequent offspring. An understanding of the molecular genetics of fragile X syndrome has resulted in the resolution of the Sherman paradox and is the first molecular characterization of a chromosomal fragile site, a finding that almost certainly will be important in understanding the cause of chromosomal rearrangements involving fragile sites. In addition, molecular details of the fragile X mutations have yielded insight into "heritable unstable elements," of which the fragile X chromosome is one of the first characterized examples. Thus a similar molecular mechanism involving a trinucleotide repeat may explain the genetics of myotonic dystrophy and spinal-bulbar muscular atrophy (Kennedy disease); it seems reasonable to assume that other genetic diseases also may result from disruption of genes by inherited unstable elements.