We have recently reported a protein sequence deduced from the retinoic acid (RA)-inducible mRNA J6 as a novel serine protease inhibitor (serpin). In this study we have reported that the J6 serpin gene is 7.7 kilobases in length and consists of five exons with an additional option. Comparison of the organization of the J6 gene and other serpin genes reveals that the structure of the J6 gene is different from the reported four serpin gene groups. Nonetheless, intron B of the J6 gene and members of the alpha-antitrypsin gene group are at the equivalent positions, suggesting that the J6 gene is more closely related to the members of alpha-anti-trypsin gene group than other serpins. To identify the RA response region, we have further examined the nucleotide sequence of the 1-kilobase 5'-flanking region of the J6 gene. The DNA sequence from position -1050 to -738 is essential for the gene activation by RA as revealed by the stable transfection experiments. Within this region, present are four GA-GATAG motifs which are the known binding sites for GATA transcription factor family. Interestingly, there is a potential heat shock element with alternate arrays of blocks XGAAX and XTTCX spanning from -88 to -59, indicating that the J6 gene perhaps is heat-inducible.