An immunoradiometric assay was used to determine serum ferritin in patients with iron overload disorders and in patients with liver disease. In patients with iron overload, serum ferritin was closely correlated in an exponential manner with quantitative measurements of storage iron; however, a different relationship applied when storage iron levels were within normal range, suggesting that circulating ferritin is in equilibrium with two functionally distinct tissue ferritin pools. High ferritin levels were common in patients both with acute and chronic liver disease, normal values being virtually confined to women and to subjects with a history of recent hemorrhage. In liver disease generally, serum ferritin varied both with the serum transaminase level and with liver iron concentration, but correlated well with neither factor separately. There was no correlation with the serum iron or total iron-binding capacity. An extremely close correlation was found between serum ferritin and an empirical index derived from the product of the serum transaminase times liver iron concentration, implying that the circulating level depended on both the degree of hepatocellular injury and liver iron store. There was a close linear correlation between the serum ferritin-transaminase ratio and liver iron concentration in all disorders studied, and this index may prove to be the most useful value for diagnostic purposes.