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Objective: To determine the role of health status, personality and coping style, on self-report health-related quality of life (QoL).Methods: Participants were HIV seropositive individuals at all disease stages from three samples (a) gay/bisexual men from the UK, (b) injecting drug users from the UK, (c) injecting drug users from Italy. All participants completed questionnaires evaluating QoL, personality, coping style and social support. Explicit models of the relationships between the measured variables based on a review of the literature were tested using structural equation modelling.Results: Health status was modestly associated with the physical but not the psychological aspects of QoL (beta = 0.44). Neuroticism was strongly associated with psychological QoL (beta = -0.73) but only weakly with physical QoL (beta = -0.21). The samples did not differ in either the pattern or the magnitude of these relationships. Mediating factors such as coping style, social support and other personality variables had only a weak influence on the role of Neuroticism.Conclusions: Neuroticism had a strong influence on health-related QoL that was independent of health status. Neuroticism was more strongly associated with the psychological aspects of QoL than health status. Coping styles and the other psychological variables assessed had only a weak mediating influence on this relationship. [ABSTRACT FROM AUTHOR]