Two measures of health-related quality of life in 65 HIV-infected individuals were compared in a cross-sectional design. The Quality of Well-Being Scale (QWB) results in a single score ranging from death to perfect health. The MOS-HIV Health Survey (MOS-HIV, 34-item version) gives scores in 11 dimensions. The QWB score distinguished subjects with AIDS from those who were asymptomatic (p = 0.027). For the seven multi-item scales of the MOS-HIV, Cronbach's alpha ranged from 0.85-0.95, indicating good internal consistency reliability. Clinical HIV-infection status was significantly associated with the dimensions of Overall Health (p = 0.002), Role Function (p = 0.022), Social Function (p = 0.037), Energy/Fatigue (p = 0.027) and Health Distress (p = 0.025). All eleven dimensions of the MOS-HIV were significantly correlated with the QWB score (Spearman's coefficient = 0.405-0.670; for all, p < 0.01) and the QWB score could be predicted from the MOS-HIV dimension scores using multiple regression. The QWB and the MOS-HIV may be useful in assessing health-related quality of life in patients infected with HIV.