Longitudinal declines in IQ among fragile X [fra(X)] males have been reported previously by several investigators. Remarkably little is known about longitudinal changes in IQ scores among fra(X) females. Previously, one cross-sectional study showed a significant negative correlation between age and IQ scores. However, a recent investigation of girls with fra(X) syndrome noted longitudinal increases in IQ scores in 8 of 11 individuals. Therefore, the purpose of this preliminary multicenter study was to determine: (1) the characteristics of longitudinal changes in IQ among fra(X) females; and (2) whether these changes were comparable to those which have been observed among fra(X) males. IQ test and retest scores for 11 fra(X) females were obtained from 3 centers: Greenwood, South Carolina; Ibaraki, Japan; and Leuven, Belgium. To ensure high reliability, only test-retest scores from the Wechsler and Stanford-Binet tests were used. Age of subjects at initial testing ranged from 5 to 35 years. Mean intertest interval was 4.5 years. In contrast to a report of longitudinal increases, we found 9/11 (82%) subjects demonstrated decreases in IQ scores. Mean decline was 9 points. Females over 18 years of age showed little or no change in IQ scores. Decreases in scores appeared to be related to initial IQ score. Females in the earlier longitudinal report were higher functioning than those in our study, which may account for the observed difference in direction of change; or, change in IQ score may be related to size of the fra(X) mutation.(ABSTRACT TRUNCATED AT 250 WORDS)