Comparison of health related quality of life (HRQOL) of patients with systemic lupus erythematosus (SLE) with other common chronic illnesses. Responses from self-administered Medical Outcomes Study Short Form-36 (SF-36) questionnaires from 90 patients with SLE, recorded in the lupus database at the University of Chicago Hospital, were analyzed. Comparative norms and domain scores for patients with other chronic diseases [hypertension, congestive heart failure (CHF), adult onset diabetes mellitus, myocardial infarction, and depression] were used and are based on the general US population. T tests were used to make comparisons. Patients with SLE were younger than patients with most reference chronic conditions except for depression. Their Physical Component Scores and Mental Component Scores were 30 +/- 10.5 and 45.1 +/- 11, respectively. SLE patients fared significantly worse than age matched norms from the general US population for women (p = 0.0001) in all 8 domains. Their quality of life was significantly worse than for those with hypertension, diabetes, or myocardial infarction in all domains (p < 0.004). Patients with CHF were no worse than those with SLE in regard to physical function, role-physical, role-emotional, and vitality. CHF patients fared significantly better in mental health, bodily pain, social functioning, and general health, compared to patients with SLE. Patients with depression were significantly impaired in role-emotional and mental health domains (p = 0.0001) compared to SLE patients, but were no worse (role-physical, vitality, and social functioning) and even better (physical function, bodily pain, and general health) in some. General health of SLE patients was significantly lower than all comparative groups. HRQOL of patients with SLE seems to be significantly worse and affects all health domains at an earlier age in comparison to patients with some other common chronic diseases.