We have determined the nucleotide sequence of the yeast HIS4 gene and its 5' and 3' flanking sequences. The protein chain has a calculated Mr-value of 87 935. Th 5' end of the HIS4 transcript maps at a position 63 bp upstream from the site of initiation of protein synthesis. The 3' end of the HIS4 transcript maps at a position approx. 118 bp after the UAG termination codon. There is no evidence for intervening sequences within the transcription unit. Functional sub-regions within the HIS4 coding frame have been identified by determining the sequence changes for various his4 mutations.