The nucleotide sequence of the human adenosine deaminase gene was determined. The gene was isolated in a series of overlapping lambda phage clones containing human germ line DNA. A total of 36,741 base pairs were sequenced, including 32,040 base pairs from the transcription initiation site to the polyadenylation site, 3935 base pairs of 5'-flanking DNA, and 766 base pairs of 3'-flanking DNA. The gene contains 12 exons separated by 11 introns. The exons range in size from 62 to 325 base pairs while the introns are 76-15 166 base pairs in size. The area sequenced contains 23 copies of Alu repetitive DNA and a single copy of an "O" family repeat. All but one of these repeat sequences are located in the first three introns or the 5'-flanking region. The apparent promoter region of the gene lacks the "TATA" and "CAAT" sequences often found in eucaryotic promoters and is extremely G/C rich. Contained within this region are areas homologous to other G/C-rich promoters, including six decanucleotide sequences that are highly homologous to sequences identified as functional binding sites for transcription factor Sp1.