Background: Self-reported health-related quality of life (HRQOL) assesses constructs that transcend laboratory-based clinical parameters. Corroboration of the hypothesized relationships between the 2 types of health indicators tie, clinical and HRQOL) could provide evidence of the validity of an HRQOL measurement tool. Objective: The purpose of this study was to evaluate the ability of scores on the mental component summary (MCS-12) and physical component summary (PCS-12) of the 12-Item Short Form Health Survey (SF-12) to discriminate between HIV-infected persons in predefined disease-severity groups based on surrogate markers. Methods: This cross-sectional study involved the collection of clinical data tie, CD4 cell count, viral load [HIV-I RNA copies/mL]) from patients' medical records and HRQOL data from the SF-12 at 2 HIV specialty clinics. The ability of SF-12 summary scores to discriminate between patients stratified by disease severity tie, CD4 cell count <200 vs greater than or equal to 200/mm(3); HIV-I RNA >55,000 vs less than or equal to 55,000 copies/mL) was assessed by receiver operating characteristic curve analysis. Results: Data were collected from 478 patients. The scores from the PCS-12 were able to discriminate between groups of patients stratified by disease severity based on CD4 cell count (P < 0.001) and HIV-I RNA copies/mL (P < 0.01). MCS-12 scores did not discriminate between disease-severity groups. Conclusions: Although the SF-12 is a brief generic measure of HRQOL, these findings provide further evidence of the validity of the SF-12 and suggest that it may be a practical way to monitor health status from the perspective of the HIV-infected patient.