The objective of this study was to evaluate the construct validity of two questionnaire-based measures of health-related quality of life (HRQL) in children undergoing cancer chemotherapy: the Health Utilities Index (HUI) and the Child Health Questionnaire (CHQ). Subjects were children hospitalised for chemotherapy. To examine construct validity: (1). a priori expected relations between CHQ concepts and HUI attributes were examined; (2). HUI and CHQ summary scores were compared to visual analogue scale (VAS) scores. Ease of completion was rated using a 5-point categorical scale and completion time was recorded. A total of 36 subjects were included. The maximum score was seen in 15 (47%) of HUI3 assessments. As predicted, CHQ body pain was moderately correlated with HUI3 pain (r=0.51), CHQ physical functioning was moderately correlated with HUI2 mobility (r=0.58) and CHQ mental health was moderately correlated with HUI2 emotion (r=0.53). Only the CHQ psychosocial subscale (and not HUI) was correlated with VAS (r=0.44). The CHQ and the HUI were both easy to use. The HUI questionnaires required less time to complete (mean=3.1, s.d.=1 min) compared with CHQ (mean=13.1, s.d.=3.4 min, P<0.0001). In conclusion, HUI and CHQ demonstrated construct validity in children undergoing cancer chemotherapy. The Health Utilities Index is subject to a ceiling effect whereas CHQ requires more time to complete.