OBJECTIVE: We compared body composition measurement in adults with cystic fibrosis (CF) by using non-invasive methods (skinfold thicknesses and bioelectrical impedance analysis [BIA]) with dual-energy X-ray absorptiometry (DXA). METHODS: Seventy-six adults with CF (mean age 29.9 +/- 7.9 y, mean body mass index 21.5 +/- 2.5 kg/m(2)) were studied. Body composition was measured to calculate fat-free mass (FFM) using DXA, the sum of four skinfold thicknesses, and BIA (predictive equations of Lukaski and of Segal). RESULTS: Mean FFM values +/- standard deviation measured using DXA were 54.8 +/- 7.3 kg in men and 41.2 +/- 3.9 kg in women. Mean FFM values measured using BIA/Lukaski were 51.5 +/- 7.8 kg in men and 40.4 +/- 4.9 kg in women (P < 0.0005 for men, not significant for women for comparison with DXA). Mean FFM values measured using BIA/Segal were 54.2 +/- 7.5 kg for men and 44.1 +/- 5.9 kg for women (not significant for men, P < 0.0005 for women for comparison with DXA). Mean FFM values measured using skinfolds were significantly higher than those for FFM with DXA (57.2 +/- 7.2 kg in men, 43.3 +/- 4.3 kg in women, P < 0.0005 for comparison with DXA). The 95% limits of agreement with FFM using DXA were, for men and women, respectively, -8.3 to 1.7 kg and -6.4 to 4.8 kg for BIA/Lukaski, -4.8 to 3.6 kg and -3.1 to 8.9 kg for BIA/Segal, and -2.8 to 7.3 kg and -1.5 to 5.7 kg for skinfolds. CONCLUSION: This study suggests that skinfold thickness measurements and BIA will incorrectly estimate FFM in many adults with CF compared with DXA measurements of FFM. These methods have limited application in the assessment of body composition in individual adult patients with CF.