Despite many technical advances in dialysis care, morbidity and mortality in chronic hemodialysis patients in the United States remains high. In this study, we analyzed the effects of Kt/V, nutritional parameters (serum albumin level, triceps skin-fold thickness, mid-arm muscle circumference, and normalized protein catabolic rate), and predialysis serum cortisol and insulin growth factor-1 levels on predicting morbidity and mortality. The cohort studied consisted of 52 patients recruited from a single outpatient dialysis facility. Cox proportional hazards modeling indicated that only Kt/V predicted subsequent mortality (P = 0.02), while both predialysis cortisol levels (P = 0.03) and Kt/V (P = 0.03) predicted hospitalization. Kaplan-Meier analysis demonstrated that the ability of cortisol levels to predict hospitalization was largely confined to the group with values greater than 22 micrograms/dL predialysis. High serum cortisol levels were correlated with low serum albumin levels and a trend toward low triceps skin-fold thickness and higher normalized protein catabolic rate, suggesting a catabolic state. Both predialysis serum cortisol and insulin growth factor-1 levels were higher than those in age- and sex-matched normal human controls. These results demonstrate the importance role of Kt/V in predicting subsequent hospitalization rates and mortality, and that high predialysis serum cortisol levels correlate with a high hospitalization rate.