The structure of the human bone morphogenetic protein-4 (BMP-4) gene has been characterized from a genomic cosmid clone of about 38 kb. The transcriptional unit of the human BMP-4 gene is encoded by 5 exons and spans approximately 7 kb. The exon-intron organization of the human BMP-4 gene is similar to that of the mouse gene, with notable sequence differences in the 5' non-coding exons. The human BMP-4 gene has at least two functional promoters, which are used in a cell type specific manner. This observation is of fundamental relevance for understanding the specific role of BMP-4 in skeletal development and bone remodeling.