OBJECTIVE: Reactive regional lymph node enlargement is a frequent ultrasonographic finding in patients with Crohn's disease. However, the prevalence of this condition and its clinical significance are unknown. This study assesses the prevalence of enlarged regional mesenteric lymph nodes and its clinical significance in Crohn's disease, and in particular whether there is a correlation between the sonographic detection of enlarged regional lymph nodes and the degree of clinical or biochemical activity of the disease. MATERIAL AND METHODS: A total of 240 in- and outpatients with Crohn's disease underwent intestinal ultrasound to assess the presence of enlarged regional lymph nodes as well as the thickness and echopattern of the bowel wall, the site and extent of Crohn's disease and the presence of stenosis, fistulas and abscesses. Demographic, clinical and biochemical parameters were also collected for each patient. A multivariate model by means of multiple regression analysis was used to identify independent variables linked to regional lymph node enlargement. RESULTS: Enlarged regional lymph nodes were detected ultrasonographically in 25.4% of Crohn's disease patients. The presence of regional lymph nodes showed a weak correlation with both clinical and biochemical Crohn's disease activity. Regional lymph nodes were found more frequently in young patients (50% of patients < 30 years, 18% of patients between 30 and 50 yrs, and 7% of patients > 50 yrs; p<0.0001) and in patients with a shorter disease duration. Enlarged regional lymph nodes were strongly correlated with internal fistulas and intra-abdominal abscesses. The multiple regression analysis showed that age, duration of disease and presence of internal fistulas were the best independent predictive factors linked to the presence of enlarged mesenteric lymph nodes. CONCLUSIONS: The sonographic detection of enlarged regional lymph nodes is more frequent in young patients, which suggests an earlier phase of Crohn's disease and the presence of septic complications such as fistulas and abscesses, but this is of limited valued in assessing disease activity.