To determine the accuracy and reliability of a labeled leukocyte imaging technique in the early diagnosis of pediatric appendicitis, we prospectively studied patients presenting to the pediatric emergency department with abdominal pain suggestive of appendicitis. Patients scheduled for urgent laparotomy were excluded, as were postmenarchal females. Blinded interpretations by two independent radiologists were compared with surgical findings, if managed operatively, or with discharge diagnoses and three week follow-up, if managed medically. Twenty-three children underwent technetium-99m hexamethylpropylene amine oxime (HMPAO) leukocyte scintigraphy. Seven had pathologically proven appendicitis, with false negative interpretations made in three and five cases by the two radiologists. Sixteen patients had prompt resolution of symptoms; however, scintigraphic abnormalities were identified in 10 and seven cases by the two radiologists. Resulting sensitivity, depending on the individual reader, ranged from 29 to 57%, with specificity 38 to 56%, positive predictive value 22 to 29%, negative predictive value 64 to 67%, and accuracy 43 to 48%. Interrater reliability for agreement on the scintigraphic diagnosis of appendicitis was poor (kappa = 0.38). Technetium-99m HMPAO leukocyte scintigraphy was neither accurate nor reliable as a diagnostic tool in a subgroup of pediatric patients with an initial clinical presentation equivocal for appendicitis. This finding contradicts previously published experience using similar scintigraphic techniques.