This longitudinal study was designed to investigate trajectories of nonverbal cognitive ability in adolescents with fragile X syndrome with respect to the relative influence of fragile X mental retardation protein (FMRP), autism symptom severity, and environmental factors on visualization and fluid reasoning abilities. Males and females with fragile X syndrome (N = 53; ages 10-16 years) were evaluated with the Leiter-R at up to four annual assessments. On average, IQ declined with age. FMRP levels predicted change in fluid reasoning, but not in visualization. The role of FMRP in the neural development that underlies the fragile X syndrome cognitive phenotype is discussed.