The genes encoding human interleukin-4 (IL-4) and interleukin-13 (IL-13) are located on segment q23-31 of chromosome 5 and encode two multifunctional lymphokines with some common functions. We have cloned 72 kb of human genomic DNA that contain IL-4 and IL-13 and their flanking sequences, and constructed a restriction map of this region. Using Southern analysis, we have shown that IL-13 is located 12 kb 5' to IL-4 and linked in a 'tail-to-head' fashion. We have also determined the complete nucleotide sequence of the DNA fragment (about 4.8 kb) containing IL-13 and its 5' flanking regulatory region (2.1 kb) with a 'CpG island'. We identified potential binding sites for a different transcription factors in the 5' flanking region and in the first intron of IL-13. Comparison of IL-13 and IL-4 revealed considerable similarity in the structural organization of these genes and also many potential binding sites for transcription factors common to both genes: AP1, AP2, AP3, PEA3, HRE, TCF-1, GATA-3 and the interferon-inducible and enhancer elements. These results, along with the similarity in functional activity of IL-4 and IL-13 suggests that their expression may be coregulated.