Background, objectives and methods This paper reports a longitudinal study of the quality of life (QOL) of outpatients receiving treatment for psoriasis in secondary care that was designed to validate a new QOL measure for use in psoriasis: the WHOQOL-100. Additional aims were to monitor the changes to the QOL of psoriasis patients (n = 83) following a course of topical treatment-a modified Ingram regimen-and to compare their QOL with healthy people (n = 105). Results General QOL was much improved following treatment; psychological facets of body image and appearance, self-esteem and negative feelings were particularly responsive to clinical change, in addition to positive feelings and cognitive capacity. Domains on spirituality, independence and physical health also improved. Compared with healthy controls, pretreatment psoriasis patients showed poorer physical, psychological, independence and spiritual QOL. Validity and reliability were investigated and found to be good to excellent. Internal consistency was very good in 23 facets out of 25. Domains and facets were strongly correlated (weaker for spirituality) largely reaffirming the WHOQOL concept. While physical, independence and psychological domains have some components similar to the Short Form-36, the social and environment domains represent novel conceptual areas for the WHOQOL. Facets about positive and negative feelings were validated by results from the Profile of Mood States. Psoriasis severity was associated with QOL in only six facets out of 25. Conclusions The WHOQOL-100 is reliable and valid, and hence a new and important measure for assessing quality of life in psoriasis.