Northern blot analyses of the poly(A)+ RNAs from human brain and liver, using a human brain ferritin heavy chain (FTH) cDNA as the probe, shows the presence of two transcripts of 1.4 and 1.1 kb. The larger, 1.4-kb RNA, is expressed predominantly in the brain, whereas the smaller, 1.1 kb, is expressed abundantly in the liver. Screening of two normal human brain cDNA libraries yielded two types of human brain FTH cDNAs. One type corresponds to the previously characterized 1.1-kb RNA from liver and lymphocytes. The other is also identical to the previously characterized FTH cDNA except that it contains an additional 279-bp sequence at the 3' untranslated region. This additional sequence shows 94.1%, 62.5%, and 58.9% identity to the 3' flanking sequence of the human liver and mouse and rat FTH genomic clones, respectively. A fragment of a genomic clone containing the 279-bp sequence was also isolated and sequenced. These data suggest that differential processing of the primary transcript for the FTH mRNA in human brain and liver could generate two mature mRNAs of 1.4 and 1.1 kb. This could be due to the use of alternative polyadenylation sites in the pre-mRNA.