Serum biochemical markers suggestive of undernutrition are directly correlated with mortality in hemodialysis and peritoneal dialysis patients. In particular, serum albumin is the most powerful predictor of survival. We have prospectively examined the relationship of single baseline measurements of serum albumin, cholesterol, creatinine, apoproteins, and prealbumin in 250 hemodialysis patients and 140 patients maintained on continuous ambulatory peritoneal dialysis (CAPD) monitored up to 7 years (1987 to 1994). Other variables studied included age, race, gender, diabetes, and number of months on dialysis. Observed survival was computed by the Kaplan-Meier method. Cox's proportional hazards model was used to determine independent predictors of mortality risk. Age, diabetes, prior months on dialysis, and low levels of serum albumin, creatinine, and cholesterol were important and independent predictors of mortality risk in hemodialysis patients. For peritoneal dialysis patients, the independent predictors of mortality risk were age, diabetes, and low serum albumin and serum creatinine. Prealbumin, a serum protein with rapid turnover and relatively small pool, was an important and independent risk predictor in both hemodialysis and CAPD patients. In addition, prealbumin was more highly correlated with other nutritional markers than was albumin. In summary, these findings suggest that biochemical measures associated with visceral and somatic protein depletion are predominant long-term mortality risk factors in patients maintained on hemodialysis and CAPD.