Background: This study considered the general validity of the basic domains of quality of life that appear in theoretical models, in relation to people with profound multiple disabilities. The authors examined how parents and direct support staff operationalized these basic domains for people with profound multiple disabilities. They investigated the effect of the support setting and age of people with profound multiple disabilities on this operationalization. Methods: A number (n = 76) of parents and direct support staff of people with profound multiple disabilities were interviewed. Transcripts were analysed in depth. Results: Results showed that the five basic domains as described within the model of Felce & Perry ["Research in Developmental Disabilities" (1995) vol. 16, pp. 51-74; "Quality of Life in Health Promotion and Rehabilitation Conceptual Approaches, Issues and Applications" (1996a) Sage Publications; "Quality of Life". "Vol. I: Conceptualization and Measurement" (1996b) American Association on Mental Retardation] were identified spontaneously by more than half of the respondents as being salient for the quality of life of people with profound multiple disabilities. When asked explicitly, this value rose to between 88.2 and 100%. The operationalization of these basic domains by parents and direct support staff differed in several aspects from operationalizations for other target groups. Neither age nor support setting turned out to have a significant effect on the operationalization. Conclusions: The results supported the multidimensionality of quality of life and the validity of the basic domains for people with profound multiple disabilities. The content of the domains of quality of life differed, however, to a considerable extent for people with profound multiple disabilities. Furthermore, these people are extremely dependent on others for the gratification of their needs and therefore for their quality of life.