We have isolated two overlapping recombinant lambda-phage clones from a genomic lambda-EMBL3 library containing 25 kb of the human lysozyme gene region. Furthermore a full-lenght human lysozyme cDNA clone of 1.5 kb was isolated from a human placenta cDNA library. Nucleotide sequences of the entire structural gene and the cDNA clone were determined. The human lysozyme gene spans 5856 bp and its sequence organization with four exons and three introns is homologous to the chicken lysozyme gene and the human alpha-lactalbumin gene. Human and chicken lysozyme genes differ mainly in the size of their introns and 3' non-coding region. Four Alu repetitive elements were found in the human lysozyme gene, one in each intron and one on the fourth exon. Lysozyme transcripts of 1.6 kb and 0.6 kb in size were detected in human myeloid cell lines U-937, HL-60 and THP-1 and surprisingly in human hepatoma cell lines HepG2 and Hep3B. The lysozyme gene locus was assigned to human chromosome 12 by hybridization to a panel of DNAs from human-rodent somatic cell hybrids.