This study reports the results of quantitative analysis of iliac bone histology in adults with cystic fibrosis (CF) and low bone mineral density (BMD). Twenty patients with CF had bone biopsies taken after double tetracycline labeling. Histomorphometric measurements were made by image analysis, and data were compared with those of healthy control subjects. Cancellous bone area was lower in the patients with CF (p = 0.003), and there was a trend towards a decrease in cancellous bone connectivity. Bone formation rate at tissue level was significantly lower in patients with CF (p = 0.0002). Wall width, representing the amount of bone formed within individual remodeling units, was decreased (p < 0.0001), as was mineralizing perimeter and mineral apposition rate. Analysis of resorption cavities revealed lower cavity area, reconstructed surface lengths, and cavity depths (p < 0.003) in patients with CF, whereas eroded surface area was higher (p = 0.0004). Our results demonstrate low cancellous bone volume in adult patients with CF with low BMD, the main cause of which appears to be low bone formation at tissue and cellular level. Osteomalacia was diagnosed in one patient. This condition should be excluded as a cause of low bone mineral density in patients with CF and vitamin D insufficiency corrected.