BACKGROUND Extreme elevation the of erythrocyte sedimentation rate (ESR >or= 100 mm/hour) is usually associated with significant diseases. This study was performed to assess its significance in pediatric patients seen in Aseer Central Hospital. METHODS All ESRs performed for children between September 2001 and December 2002 were reviewed. The medical records of those with an ESR>or=100 mm/hr (group 1) were reviewed for age, sex, diagnosis, ESR value, hemoglobin (Hgb) value and leukocyte counts. The diagnoses were divided into seven categories: malignancy, connective tissue diseases (CTDs), tropical infections, mild infections, severe infections, renal diseases and miscellaneous. One hundred forty-five patients with an ESR<100 mm/hr (group 2) were randomly selected for comparison. RESULTS Of 2540 ESRs, 99 were >or=100 mm/hr (3.9%). There were 54 males and 45 females and the mean age was 72+/-48.2 months. Infection was the most common cause (49.5%), followed by CTDs (26.3%), malignancy (12.1%) and renal diseases (8.1%). Malignancy was associated with the lowest Hgb value (8.2 g/dL). A comparison between group 1 and group 2 considering each diagnostic category separately showed that group 1 patients with mild infections had significantly higher mean leukocyte counts and that group 1 patients with CTDs had significantly lower Hgb values than group 2 patients with the same diagnoses, but there were no significant differences between the other diagnostic categories. CONCLUSIONS The most common cause of extreme elevation of ESR is infection. This extreme elevation may be used as a sickness index, but not as a screening tool for any disease.