This study was designed to measure the health-related quality of life of a sample of diabetic Pima Indians. Health status questionnaires were administered to 54 diabetic Pima Indians attending an outpatient pharmacy in southern Arizona. Health-related quality of life was assessed using the SF-36 Health Survey. Internal consistencies of the eight multi-item scales of the SF-36 were estimated. Nonparametric analyses were performed to determine relationships between mean SF-36 scale scores and various clinical and demographic variables. Favorable internal consistencies for the multi-item scales were observed, with alpha coefficients ranging from 0.63 to 0.91. SF-36 scale scores were not influenced by sex or education level. Age was significantly associated with four of the eight dimensions. Indicators of glycemic control were not significantly associated with any SF-36 multi-item scale scores. Subjects with more comorbid chronic conditions had significantly lower SF-36 scores. If the goal of maximizing health status of American Indians is to be reached, health-related quality-of-life assessment should be used as a means to monitor progress toward that goal. Further evaluation of the SF-36 or other health status/quality-of-life instruments in this population should be undertaken.