Multiple reports have demonstrated the benefit of growth hormone (GH) treatment in children with cystic fibrosis (CF) and previous studies have demonstrated low to normal insulin-like growth factor-I (IGF-I) levels in these patients. Most biological effects of GH are mediated by IGF-I; however, the relationship between height, weight and rate of growth has not been systematically studied in CF. We conducted a retrospective analysis of 52 patients (including control volunteers with CF) who had participated in previous studies of GH treatment to determine the relationship between levels of IGF-I and growth in children with CF. In a subset of these patients, we also evaluated the relationship between protein catabolism and IGF-I. Baseline IGF-I levels and IGF-I z-scores were correlated with same day measures of height, weight, height and weight z-scores. In a subset of patients, IGF-I levels were also correlated with leucine rate of appearance (a measure of protein catabolism). IGF-I levels were obtained every six months during our studies and were correlated with same day height, weight and protein turnover. Height and weight velocity were calculated every six months from study baseline and were correlated with IGF-I levels. In all patients, whether treated with GH or controls, we found a positive linear correlation between IGF-I levels and height (r = 0.66, p < 0.0001) and weight (r = 0.61, p < 0.0001), as well as height and weight velocity. There was also a strong relationship between leucine rate of appearance and IGF-I. These results suggest a strong correlation between IGF-I and height, weight and protein catabolism and emphasize the need to normalize IGF-I levels in children with cystic fibrosis.