Chronic fatigue syndrome (CFS) is a controversial diagnosis with unknown cause. Adult studies indicate high rates of psychosocial dysfunction and psychiatric comorbidity. The authors compared three groups of pediatric patients selected by diagnosis-(1) CFS (n = 15), (2) juvenile rheumatoid arthritis (n = 15), and (3) mood disorders (n = 15)-across many psychological measures. CFS subjects had dramatic elevation of the Somatic Complaints subscale (mean T score = 75), whereas the mood disorders group had higher externalizing scores (mean T score = 68) on the Child Behavior Checklist. The CFS subjects missed significantly more school compared with the two control groups. After the onset of CFS, 13 of 15 of the CFS patients required significant educational accommodation. Only 4 of the 15 CFS patients had an Axis I psychiatric diagnosis, as determined by the Computerized Diagnostic Interview for Children. Despite a low rate of psychiatric diagnosis in the CFS sample, these data attest to their psychosocial and school dysfunction.