Growth failure and altered body composition is known to occur in children with CF, but the longitudinal age and gender-related pattern of these changes has not been described previously. This study examined prospectively the growth and body composition of 25 prepubertal children with CF (initially 5-10 yrs of age) and 25 healthy controls of comparable age, gender and weight. All children with CF were pancreatic insufficient, had mild pulmonary disease and had initial ht and wt above the 5th percentile. Subjects were evaluated four times at yearly intervals while in their usual state of good health. Body composition was determined by anthropometric evaluation of wt, ht, and skinfold thicknesses at the biceps, triceps, subscapular, and suprailiac sites. Wt and ht z-scores were calculated from NCHS reference data. Longitudinal comparisons between groups were performed using longitudinal mixed effects analysis. Statistical significance was defined at the p<0.05 level. On average, the wt and ht z-scores for the CF group were lower than for the controls. The ht z-scores of CF boys were significantly lower than that of the control boys, while the girls in the CF and control groups were similar. Fat free mass (FFM) significantly increased over the 3 yr period for boys and girls in both groups. For boys with CF, FFM was consistently lower than for the control boys. The gap in FFM between the CF and control boys significantly increased over time. In contrast, the girls with CF had slightly higher but not significantly different FFM than the control girls over time. Fat mass(FM) increased over the 3 yr period for both the CF and control groups. The pattern of FM over time was different between the boys and girls. Both groups of girls expressed significant increases in FM over time, however, there were no increases in FM in the two groups of boys. The boys with CF had lower FM than the control boys, with the disparity in FM getting larger with time, while the girls with CF more closely patterned the FM of the control girls over time. These findings demonstrate that the longitudinal patterns of growth and body composition are different between boys and girls with CF. In this age range, the growth and nutritional status of boys with CF failed to keep up with that of healthy control boys, with growth disparities increasing with time. In contrast, this sample of young girls with CF closely matched the growth patterns of healthy control girls over time.