We have determined the complete nucleotide sequence of a Synechococcus sp. PCC7942 gene encoding the homologue of mammalian uroporphyrinogen decarboxylase (UROD). The gene, designated hemE, encoded a polypeptide of 354 amino acids with a molecular weight of 39,283. The primary sequences of the polypeptide encoded by hemE and human and rat UROD had 32.5% identical amino acid residues. No invariant cysteine residues were found, despite the fact that UROD isolated from different sources has been shown to be inhibited by sulfhydryl reagents. The knowledge of the primary structure of this cyanobacterial protein may be helpful in better understanding the structural alterations and functional abnormalities of UROD in patients suffering from Porphyria Cutanea Tarda (PCT).