The purposes of this study were to measure health-related quality of life in the Modification of Diet in Renal Disease clinical trial; correlate quality of life measures with demographic, medical, and laboratory variables; and compare quality of life in various chronic diseases. The 1,284 patients enrolled in the baseline period of the Modification of Diet in Renal Disease study who completed at least one measurement of quality of life or symptoms served as the subjects of this study. The Quality of Well-Being (QWB) scale, which was a general health-related quality of life index, the Symptom Checklist-90R (SCL-90R), which provided a global measure of mental health, and the Patient Symptom Form, which assessed the frequency of symptoms specific to this population, were used as measurements. The mean +/- SD QWB score was 0.74 +/- 0.09. Using multivariate analysis, there was a significant negative correlation between the overall QWB score and age and female gender, and a significant positive correlation between the QWB and level of education, income, and glomerular filtration rate (GFR). For the SCL-90R subscores, the mean normalized Global Symptom Index was 49.7 +/- 9.6, the Positive Symptom Total was 47.9 +/- 10.4, and the mean Positive Symptom Distress Index was 51.3 +/- 12.6. Using multivariate analysis, significant inverse relationships were seen between each of the SCL-90R subscores and income, serum albumin level, and GFR. The most commonly reported medical symptoms in this cohort included tiring easily, weakness, lack of pep or energy, difficulty sleeping, and abdominal bloating or gas. Symptoms in which the severity index score had a negative correlation with GFR included tiring easily, weakness, lack of pep and energy, muscle cramps, easy bruising or bleeding, bad taste in mouth, and hiccoughs. In conclusions, patients with moderate to advanced renal insufficiency have a reduced quality of life and an increased frequency and severity of both symptoms and psychological distress, with the magnitude of these changes negatively correlated with GFR.