Although interest in the health-related quality of life (HRQOL) of children has increased in the last years, validated methods for assessing the HRQOL- and especially the perceived HRQOL-of children have been missing. We introduced a 17-dimensional, illustrated, generic measure of perceived HRQOL (17D) for pre-adolescents, and demonstrated its application to three populations of children aged 8-11 years: (1) 244 normal schoolchildren; (2) 22 patients surviving organ transplantation and (3) 10 patients with genetic skeletal dysplasias. The HRQOL scores and profiles of the patients differed significantly according to the diagnosis, giving support to its construct validity. The reliability of the measure was high: its repeatability coefficient was 95%. As a structured interview of 20-30 minutes, the measurement burden is reasonable. We conclude that the assessment of quality of life of pre-adolescents can and should be based on data collected from the children themselves. Our initial experience indicates that 17D is comprehensive, reliable, and valid.