Objective: to evaluate the psychometric performance of a new human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS)-targeted quality of life (QoL) instrument in asymptomatic HIV-seropositive individuals. Methods: 201 urban and rural, HIV-seropositive subjects were recruited to complete a 76-item pilot QoL measure developed using content provided in group process by seropositive individuals. Questionnaire responses from the full sample (n=201) were used to identify dimensions and to reduce the number of items to 42. The responses to the retained items were then analysed for the asymptomatic subsample (n=106). Results: 9 multi-item dimensions were identified: overall function (OF), sexual function (SF), disclosure worries (DW), health worries (HW), financial worries (FW), HIV mastery (HM), life satisfaction (LS), medication concerns (MC) and provider trust (PT). The responses by asymptomatic subjects (74% male, 64% non-White and 63% homosexual/bisexual) revealed no substantial floor or ceiling effects, except for the PT dimension (where 44% were found to have scored the highest score). The internal consistency coefficients (Cronbach's alphas) were between 0.80 and 0.89 for six dimensions. The coefficients were lower for the SF (0.52), HM (0.67) and MC (0.48) dimensions. Construct validity assessments, using self-reported HIV disease-severity and sociodemographic variables, revealed some significant relationships (p≤0.05) for all dimensions except SF, MC and PT. Conclusions: the results suggested that five dimensions (OF, DW, HW, FW and LS) from the new instrument have good psychometric properties for asymptomatic HIV-seropositive individuals. These dimensions may be useful in the study of asymptomatic, seropositive individuals' QoL. Four dimensions (SF, HM, MC and PS) require additional refinement for this subpopulation.