Purpose: Although acute nonspecific mesenteric lymphadenitis (ANML) is probably common cause of abdominal pain in children, which can be severe enough to be an abdominal emergency, the clinical features of mesenteric lymphadenitis are not clear. Also, a differential diagnosis with acute appendicitis (APPE) is indispensable to avoid serious complications. The clinical features of ANML were determined, and the risk factors for differential diagnosis with APPE were analyzed. Methods: Between November 2000 and May 2001, data from 26 patients (aged 1 to 11 years) with ANML and 21 patients (aged 2 to 13 years) with APPE were reviewed. ANML was defined as a cluster of five or more lymph nodes measuring 10 mm or greater in their longitudinal diameter in the right lower quadrant (RLQ) without an identifiable specific inflammatory process on the ultrasonographic examination. There were risk factors on patient's history, physical examination, and laboratory examination; the location of abdominal pain, abdominal rigidity, rebound tenderness, fever, nocturnal pain, the vomiting intensity, the diarrhea intensity, the symptom duration, and the peripheral blood leukocytes count. Results: Of the 26 ANML patients and 21 APPE patients, abdominal pain was noted on periumbilical (76.9% vs 14.2%), on RLQ (11.5% vs 71.4%), with abdomen rigidity (7.6% vs 80.9%), with rebound tenderness (0.0% vs 76.1%)(p<0.05), in the lower abdomen (11.5% vs 14.2%), and at night (80.8% vs 100.0%) (p>0.05). The clinical symptoms were vomiting (38.4% vs 90.4%), the vomiting intensity ($1.5{\pm}0.7$ [1~3]/day vs $4.5{\pm}2.9$ [1~10]/day), diarrhea (65.3% vs 28.5%) (p<0.05), and fever (61.5% vs 76.2%)(p>0.05). The period to the subsidence of abdominal pain in the ANMA patients was $2.5{\pm}0.5$ (2~3) days. The laboratory data showed a significant difference in the peripheral blood leukocytes count ($8,403{\pm}1,737[5,900{\sim}12,300]/mm^3\;vs\;15,471{\pm}3,749[5,400{\sim}20,800]/mm^3$)(p<0.05). Discriminant analysis between ANML and APPE showed that the independent discriminant factors were a vomiting intensity and the peripheral blood leukocytes count and the discriminant power was 95.7%. Conclusion: The clinical characteristics of ANML were abrupt onset of periumbilical pain without rigidity or rebound tenderness, a mild vomiting intensity, normal peripheral leukocytes count, and relatively short clinical course. If the abdominal pain persist for more than 3 days, and/or the vomiting intensity is more than 3 times/day, and/or the peripheral leukocytes count is over $13,500/mm^3$, abdominal ultrasonography is recommended to rule out APPE.