Depressive symptoms of at least moderate severity were reported by more than 25% of a consecutive sample of end-stage renal disease (ESRD) patients awaiting cadaveric transplantation. Subjects with depressive symptoms in the clinically significant range were more often unemployed and were more functionally disabled than subjects with depressive symptoms of lesser severity. Depressive symptoms and functional disability were significantly correlated at lower but not higher levels of depression. Although depressed medical patients tend to be more impaired than those who are not depressed, the occurrence of depressive symptoms of clinical severity may depend upon the interaction among multiple additional factors. Clinically significant depression is not inevitable with severe medical disabilities and its occurrence should draw attention to specific individual vulnerabilities.