The genomic clone of mouse IL-6 was isolated and compared with the human IL-6 gene. The comparison revealed that the mouse IL-6 consists of five exons and four introns and that the overall organization is similar to that of the human IL-6 gene although the third intron is about 2 kb longer. The sequence similarity in the coding region is about 60%, whereas the 3'-untranslated region and the first 300-bp sequence of the 5'-flanking region are highly conserved (greater than 80%). Several sequence blocks with high homology are also found in the introns. Furthermore, sequences similar to transcriptional enhancer elements such as the c-fos serum responsive element and the consensus sequences for cAMP induction, activator protein 1 binding, and the glucocorticoid receptor binding are identified within the highly conserved 5'-flanking regions of the genes from the two species. These sequences may play an important role in transcriptional activation of the IL-6 gene.