A highly sensitive thin layer chromatographic assay was used to establish distinct anomalies in hepatic and renal prophyrin synthesis associated with chronic renal failure. Urinary and plasma coproporphyrin disappeared but plasma uroporphyrin (isomer III) levels rose. Patients on maintenance hemodialysis showed elevated red cell protoporphyrin and decreased total stool porphyrins whilst the raised plasma uroporphyrin did not pass into the dialysate, even in 2 cases of overt symptomatic porphyria. These results indicate that urinary coproporphyrin is of renal and not hepatic origin and that azotemia may reduce the activity of the enzyme uroporphyrinogen decarboxylase.