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The objectives of this study were to identify quality-of-life concerns, as reported by human immunodeficiency virus (HIV) seropositive individuals, and to develop a measure to assess these concerns.The HIV/acquired immunodeficiency syndrome (AIDS)-targeted measure was developed in two linked studies. In study one, group discussions with 42 HIV seropositive individuals were used to generate item content for the new measure. In study two, 201 HIV seropositive individuals were cross-sectionally studied to identify dimensions and to reduce the number of items of the quality of life questionnaire resulting from study one.Study one subjects (76% male; 66% white; 55% gay/bisexual) identified concerns captured by 76 items. Factor analysis indicated that responses of study two subjects (78% male; 42% white; 55% gay/bisexual) could be summarized by nine dimensions. Overall function, sexual function, disclosure worries, health worries, financial worries, HIV mastery, life satisfaction, medication concerns, and provider trust dimensions were refined by removing items using methods to maximize internal consistency and to minimize item redundancy. No substantial ceiling/floor effects existed, except for the provider trust dimension (43% received the highest score possible). All internal consistency coefficients were ≥0.70, except those for the HIV mastery (0.57) and medication concerns (0.51) dimensions, as well as the sexual function dimension (0.56) in the non-AIDS subsample. Multitrait/multiitem assessment indicated scaling success rates that were high (≥91%) for eight of nine dimensions (HIV mastery revealed a lower but modest success rate of 79%). Validity assessments, using self-reported HIV disease severity and sociodemographic variables, indicated expected relationships for all dimensions.Five dimensions of the new HIV/AIDS-targeted quality of life instrument (overall function, disclosure worries, health worries, financial worries, and life satisfaction) exhibited good psychometric properties, including low ceiling/floor effects, good internal consistency, and evidence for construct validity.