This study examined the trajectories of cognitive development in boys under the age of 21 years with fragile X syndrome. By combining information from three centers, data from 66 boys were analyzed; only children who had been tested two or more times with the same psychometric instrument at one or more year intervals were included in this study. Results demonstrated that males with fragile X syndrome show a decline in IQ scores, with the most marked declines seen during the early pubertal period. All 22 children retested during the 11- to 15-year period showed IQ declines, suggesting a slowing of development associated with the onset of puberty. Before age 10 years, males with higher (as opposed to lower) pretest IQs were more likely to decline at subsequent testings. A single etiological factor may not be sufficient to account for the observed findings, as both changes in neurobiological- and task-related factors seem implicated in the slowing intellectual development of this population.