OBJECTIVE Infertility in patients with cystic fibrosis has been attributed to the congenital bilateral absence of the vas deferens. We studied the vas deferens in cystic fibrosis fetuses to determine whether this condition could be related to primary developmental abnormalities or to secondary obstructions. METHODS Two cystic fibrosis male fetuses, with deltaF508+/+ and deltaF508/G542X genetic mutations, were examined after abortion at 12 and 18 weeks, respectively. The lumens of the vas deferens were measured using histological serial sections in the 2 cystic fibrosis fetuses and in 6 control fetuses. RESULTS The vas deferens of cystic fibrosis and control fetuses showed a similar development. The diameters of the lumens were smaller at the extremities than in the medial part of the duct in cystic fibrosis and in control fetuses. No epithelial necrosis, focal dilatation or fibrous stenosis could be detected at any age. Secretions were observed in the lumen of the vas deferens of the homozygous fetus, but no obstruction was detected. CONCLUSIONS The normal organogenesis of the vas deferens, the presence of secretions filling the lumen of the deltaF508 +/+ fetus and the high proportion of normal ducts reported in prepubertal male cystic fibrosis patients suggest a mechanism of luminal obstruction resulting in duct atrophy and infertility in male adults with cystic fibrosis. The term "atresia" or "inspissation" should be used in cases of congenital bilateral absence of the vas deferens associated with cystic fibrosis mutations, whereas the term "agenesis" should be used for cases of congenital bilateral absence of the vas deferens associated with urogenital abnormalities in which regional defects occur during organogenesis.