Transferrin is a major plasma protein that transports iron to proliferating cells throughout the body. A clone containing the 5' region of the human transferrin gene has been isolated and characterized. A 14 kb EcoRI fragment was identified that contained the first 8 exons of the transferrin gene and 3.6 kb of its 5' flanking region. Conserved sequences identical or homologous to regulatory elements responding to heavy metals, glucocorticoid receptor and a putative acute phase reaction signal were identified in the 5'flanking region and intron 1. Also, the regulatory region of the transferrin gene contains a 14-bp sequence which closely matches sequences found in the interleukin-2 and gamma-interferon genes. All three genes are expressed by T lymphocytes before proliferation. A secondary loop structure similar to that proposed for the ovotransferrin gene can be formed by sequences in the 5' untranslated region of the transferrin mRNA.