OBJECTIVE To identify conditions associated with enlarged mesenteric lymph nodes in children with acute abdominal pain and determine the ability of US to detect associated abnormalities. METHODS Two hundred and fifty children with acute abdominal pain were evaluated for the presence of enlarged mesenteric lymph nodes (AP diameter > 4 mm). Additionally, a reference group of 50 asymptomatic children was also studied for the presence of enlarged mesenteric lymph nodes. RESULTS Enlarged mesenteric lymph nodes were noted in 35 (14%) symptomatic children and two (4%) asymptomatic children. A specific diagnosis was established in 16/35 (46%) symptomatic children with mesenteric lymphadenopathy. Acute appendicitis was the most common diagnosis. The discharge diagnosis in the remaining 19 children was abdominal pain or gastroenteritis of unknown origin. US suggested the correct diagnosis in 12/16 (75%) children in whom a definite diagnosis was established. Histopathologic examination of enlarged mesenteric lymph nodes in three patients demonstrated non-specific inflammatory changes. CONCLUSIONS Enlarged mesenteric lymph nodes in children with acute abdominal pain represents a nonspecific finding. Mesenteric lymphadenopathy is associated with a variety of medical and surgical conditions in symptomatic children and is occasionally seen in asymptomatic children. Sonography is useful in establishing a primary diagnosis in these children.