The existence of an alternative route of excretion for creatinine in subjects with chronic renal failure has been demonstrated. The data presented in this study confirm the hypothesis that creatinine is converted into other metabolites, probably by action of the gut flora. Creatinine degradation was quantitated in a group of subjects that spanned a wide range of kidney functions from normal to no renal function. Five patients were analyzed who were on maintenance dialysis, five were predialysis and two subjects were normal with respect to kidney function. Creatinine degradation expressed as a percentage of production varied from 13.9 to 27.7% in the dialysis patients, 0 to 42.3% in the pre-dialysis patients and was 0% in the controls. Creatinine degradation was correlated with plasma creatinine degradation was correlated with plasma creatinine levels in predialysis (r = 0.73, p less than 0.01), but not in dialysis patients. No correlation was found between creatinine degradation and production in either group. It is concluded that significant amounts of creatinine are degraded in dialysis patients, and this removal mechanism must be accounted for in models of the patient-artificial kidney system.