A large amount of renin mRNA was found to be expressed in the juxtaglomerular cell (JGC) tumor, as determined by Northern analysis. We have isolated the long 5'-flanking region of the human renin gene from the tumor, and characterized the promoter region with respect to nucleotide (nt) sequence and mRNA transcription start point. Of two sets of CAAT and TATA box at 29 bp upstream from the capping site is demonstrated to be a functional promoter by the primer extension. The 1:6-kb sequence, containing the 5'-flanking region, exon 1, and part of the first intron, obtained from the tumor was in complete agreement with that of the clone from fetal liver, which does not produce renin. This indicates that abnormal expression of the human renin gene in the JGC tumor involves no major alteration in the primary structure within 1.2 kb of the 5'-flanking region. Within 1.2 kb of the 5'-flanking region, there are several nt segments exhibiting homology with the glucocorticoid, estrogen, and progesterone receptor-binding sites and enhancers. These structures may be related to the tissue-specific expression of the renin gene.