The health-related quality of life of 170 adult insulin-dependent diabetic patients was measured cross-sectionally to compare a disease-specific instrument, Diabetes Quality of Life (DQOL) questionnaire, and two generic instruments, the Duke Health Profile (DUKE) and the General Health Perceptions Questionnaire (GHP). The generic measures provided as much or more information about health-related quality of life as the disease-specific instrument. This was demonstrated both by comparison of the DQOL with the DUKE and GHP and by comparison of the disease-specific with the generic components of a modified version of the DQOL. Patients with the diabetic complication of nephropathy had increased worry over their health and lower general health perceptions. Neither the duration of diabetes nor the intensity of insulin therapy, however, was found to have a statistically significant effect on any of the health-related quality of life scores. Nondiabetic factors, such as the comorbidity, nondiabetic medications, marital status, social relationships, and family arguments were found to be predictors of health-related quality of life more often than the diabetic factors duration of diabetes, complications, and intensity of insulin therapy. These analyses suggest the clinical value of using generic questionnaires to measure health-related quality of life and psychosocial factors to identify nondiabetic problems that might respond to intervention, thereby potentially enhancing the effect of diabetes-specific therapy.