We report that the human gene coding for the heparin-binding growth factor pleiotrophin (PTN) spans more than 65 kb and contains at least 7 exons. Analysis of human genomic DNA fragments showed that the open reading frame (ORF) is located on 4 exons. The splice sites in the ORF coincide with the boundaries of functional domains in the human PTN protein and appear to be conserved in the mouse PTN and in the related family of midkine genes. The 5'- and the 3'-ends in the untranslated regions of the human PTN are distinct from those of other species and are highly homologous to the antisense cDNAs of heat shock protein 70 and of ribosomal protein L7 respectively. These two regions are located on separate exons and could play a role in the posttranscriptional regulation of human PTN gene expression.