Recent research suggests that patients' perceptions may be more important than objective clinical assessments in determining quality of life (QOL) for patients with end-stage renal disease (ESRD). We interviewed 165 hemodialysis patients from 3 sites using a QOL questionnaire that included the Satisfaction With Life Scale (SWLS) and the McGill QOL (MQOL) scale, which includes a single-item global measure of QOL (Single-Item QOL Scale [SIS]). The MQOL scale asks patients to report their most troublesome symptoms. We also initiated the use of a Support Network Scale and a Spiritual Beliefs Scale. Mean patient age was 60.9 years, 52% were men, 63% were white, and 33% were African American. Patients had a mean treatment time for ESRD of 44 months, mean hemoglobin level of 11.8 g/dL (118 g/L), mean albumin level of 3.7 g/dL (37 g/L), and mean Kt/V of 1.6. Forty-five percent of patients reported symptoms. Pain was the most common symptom (21% of patients). There was an inverse relationship between reported number of symptoms and SWLS (P < 0.01), MQOL scale score (P < 0.001), and SIS (P < 0.001). The Spiritual Beliefs Scale correlated with the MQOL scale score, SWLS (both P < 0.01), and SIS (P < 0.05). The Support Network Scale score correlated with the MQOL Existential (P = 0.01) and MQOL Support (P < 0.01) subscales. No clinical parameter correlated with any measure of QOL, spiritual beliefs, or social support. Symptoms, especially pain, along with psychosocial and spiritual factors, are important determinants of QOL of patients with ESRD. Additional studies, particularly a longitudinal trial, are needed to determine the reproducibility and utility of these QOL measures in assessing patient long-term outcome and their association with other QOL indices in larger and more diverse patient populations.