A role of depression in affecting outcome in patients with end stage renal disease (ESRD) has been suggested but few have assessed psychological parameters and medical factors thought to influence survival simultaneously and prospectively. To assess whether depression or perception of illness influences survival in patients treated for ESRD, we prospectively evaluated fifty-seven patients with ESRD treated with hemodialysis (HD, n = 43) or continuous ambulatory peritoneal dialysis (CAPD, n = 14). Patients were interviewed and completed the Beck Depression Inventory (BDI) and the Illness Effects Questionnaire (IEQ). An ESRD severity coefficient was used to measure chronic illness severity. A cognitive item subset of the BDI (CDI) was used as an additional measure of depression. One and two years later, records were examined to determine survival. When initial results of the assessment of survivors and non-survivors were compared, at one year follow-up, there were no differences in mean age, duration of dialysis, severity scores, BDI or IEQ scores. The initial mean CDI scores in the group of non-survivors, however, were significantly greater than the scores in the survivor group. At two year follow-up, CDI scores were significantly different between groups, and were significant in a hazards regression. Disease severity, age and duration of dialysis were also significantly related to mortality at two year follow-up. We conclude cognitive depression is an important, early, indicator of grave prognosis in patients treated for ESRD. Early recognition of and therapeutic efforts directed toward the treatment of depression might modify outcome in ESRD patients.