Fragile X syndrome is the most common inherited cause of mental retardation, and unintelligible speech is a very common characteristics of young males with fragile X syndrome (FXS). It is unclear what aspects of speech (e.g., rate, prosody, oral structure/function, articulation, phonological processes) cause poor intelligibility. Furthermore, it has not been determined what is the role of motor speech/FMR1 protein (FMRP) levels, cognitive/linguistic factors, and the communicative context in affecting intelligibility of conversational speech of males with FXS. Identifying these factors is important because the ability to be understood is critical for effective communication, and poor speech intelligibility compromises all aspects of daily verbal interactions. The proposed research will examine longitudinally over a five year period the factors that affect changes in the speech intelligibility of 6 to 12 year old males with FXS in comparison to developmental age matched males with Down syndrome (DS) and males who are typically developing (TD). It will identify if motor speech/FMRP levels, cognitive/linguistic factors, and the social demands of the communicative context affect speech intelligibility. Sixty males with FXS between 8 and 12 years of age, 40 males with Down syndrome between 8 and 12 years of age and 40 typically developing males matched for nonverbal intelligence age will be followed for five years. Speech production in isolated words, imitated sentences, spontaneous conversational speech, and narratives will be examined for prosodic and segmental features, phonological processes, and speech intelligibility for the three groups. In addition, children’s oral motor skills, phonological processing, and selective listening will be examined. Fragile X DNA testing and FMRP analysis from blood samples will be done only on males with FXS. Growth curve methods will be used to quantify patterns of change over time in the overall level and rate of speech development including speech intelligibility.