The role of leptin in states of negative energy balance such as cystic fibrosis (CF) has not been explored. We hypothesized that leptin levels in patients with CF would be low due to correlation with body weight. Despite the importance of IGF-I in normal growth and anabolism, there are few data on IGF-I in CF. We studied 27 CF patients (25+/-5 yrs, 57+/-9 kg, 10M/17F) and 12 control subjects (25+/-4 yrs, 57+/-9 kg, 6M/6F). Each subject underwent analysis of lean body mass (LBM) and percent body fat by dual-energy x-ray absorptiometry (DEXA). Serum leptin and IGF-I levels were measured by radioimmunoassay. Serum leptin levels were similar both in CF and in controls (CF=5.3+/-4.1 ng/ml, C=4.4+/-3.6ng/ml; p=0.3), and there was no difference in percent body fat between the two groups (CF=26+/-13%, C=21+/-7%; p=0.3). Leptin levels were significantly lower in CF males than females corresponding to lower fat levels in males in both CF and controls. Leptin levels were positively correlated with percent body fat both in CF and controls (CF: r=0.8; p=0.01, CONTROL: r=0.8; p =0.2). Serum IGF-I levels were significantly lower in CF patients than in controls (CF=1.13+/-0.41 ng/ml, C=6.72+/-3.62 ng/ml; p=<0.01). We conclude that the physiological regulation of leptin is maintained in relation to body fat even in chronic illness and that the negative energy balance in CF is not caused by high leptin levels.