Objective: To determine prospectively the relationship among growth, nutritional status, and pulmonary function over a 4-year period in a large cohort of children with cystic fibrosis (CF). Study design: CF Foundation National CF Patient Registry data collected from 1991 to 1995 for 968 children (507 male) aged 5 to 8 years with pancreatic insufficiency and forced expiratory volume in 1 second within 60% to 140% of predicted values (FEV₁%) were analyzed longitudinally. Variables hypothesized to affect FEV₁% included age, sex, z scores for height, weight, percent of height-appropriate body weight, and annual number of days hospitalized. Results: The significant decline in FEV₁% was curvilinear and dependent on baseline FEV₁%; children with initial FEV₁% ≥90 declined 2.6 U/y more than those with initial FEV₁% <90. Boys gained but girls declined in z scores for height. Girls decreased in z scores for weight at a greater rate than boys. The z scores for weight and percent of height-appropriate body weight were significantly associated with longitudinal changes in FEV₁%, after adjustment was done for hospitalizations. Conclusions: Growth, nutritional status, and pulmonary function are not stable in prepubertal children with CF and pancreatic insufficiency. Important sex-related differences in growth occur before puberty. Growth and nutritional status are associated with changes in FEV₁%, suggesting that nutritional intervention may slow the decline in pulmonary function in children with CF. (J Pediatr 2000;137:374-80)