Measurement of quality of life is crucial to assess the full impact of antiretroviral therapy on patient morbidity. No quality of life instruments have been validated in an Asian HIV-infected patient population, but it is important to do so given the increasing involvement of the region in clinical trials. We set out to validate the Medical Outcomes Study HIV Health Survey (MOS-HIV) in HIV infected patients in Singapore. Clinically stable outpatients were asked to complete the 30-item MOS-HIV (English or Chinese translation). Patients were also asked about the frequency of selected disease symptoms, and clinical and demographic data were recorded from the case sheet. 163 patients (90% Chinese, 96% male, mean age 38 years, mean CD4 count 159 cells/mm(3)) participated in the study and completed the questionnaire to a satisfactory standard. The questionnaire showed good internal consistency (Cronbach's alpha >0.7 in all cases). There were significant differences in quality of life scores between Centers for Disease Control disease stages, and significant correlations with CD4 count and symptom score, confirming the discriminant validity of the MOS-HIV. Factor analysis revealed two components corresponding to physical and mental health which were similar to those of studies in Western countries except that pain was more closely related to mental than physical health. Linear regression analysis identified symptom burden as the major predictor of physical and mental health. We concluded that the MOS-HIV is a valid measure of quality of life in this HIV patient population in Singapore, and is therefore likely to be useful in future clinical trials in the region. In the era of chronic HIV disease, close attention to symptoms (disease or drug-related) is warranted due to their major adverse influence on mental and physical aspects of quality of life.