This study aimed to describe the results of findings from data collected with an HIV-specific health-related quality of life tool, and to examine the relationship between clinical and biological factors and health-related quality of life (HRQL). Data were collected as a cross-sectional, patient-completed assessment of health-related quality of life. Laboratory data were abstracted from the medical chart. Patients (n = 318) with HIV infection including asymptomatic (37%), ARC (20%), AIDS (25%), and AIDS with cancer (18%) were receiving health services at one of the medical centres serving HIV-infected patients in the Los Angeles community, including UCLA, community physicians, Veterans Affairs Medical Centers, and a county hospital. Additional data were contributed by the Johns Hopkins University Medical Center CMV Retinitis Clinic. Symptomatic patients and patients with the lowest CD4 counts reported poorer HRQL than asymptomatic patients and patients with higher CD4 counts. However, medical and demographic variables explained only 35% of the variability of HRQL ratings in this sample of HIV-infected patients. While clinical status and Karnofsky performance status may be used to estimate the impact of HIV infection on HRQL, they are not a substitute for independent assessment of HRQL by the patient.