Normal liver ferritin is composed of basic isoferritins with a greater proportion of liver (L) type. Hepatocellular carcinoma (HCC) contains, in addition, acidic isoferritin with H heart myocardium (H) type similar to that in normal adult heart myocardium, early gestation fetal liver, early placenta, HeLa cells, and tumors. Using antisera to liver and myocardial ferritin, immunohistochemical basic and acidic isoferritins, respectively, were studied in 36 HCCs. There was no significant difference in the frequencies of liver ferritin in 17 (47%) tumors and of myocardial ferritin in 22 (61%) (P = 0.3). Ten (28%) tumors showed neither basic nor acidic isoferritin, and nine (25%) had acidic but not basic isoferritin. Raised serum ferritin levels in HCC patients probably, in part, reflect ferritin secretion by the tumor. The actual serum level would then consist of a mixture of basic and acidic (possibly tumor-specific) isoferritins. Thus, diagnostic use of a serum assay which utilizes antiserum to liver ferritin will demonstrate only basic isoferritins and probably will not detect raised serum levels in approximately half of HCC patients.