The hst-2 gene was previously identified by its close homology to the hst-1 gene. Cosmid clones containing the hst-2 gene were cloned from a normal human genomic library. Focus-forming activity was observed for the hst-2 cosmids when NIH3T3 transfection assay was performed in a serum-free medium, whereas induction of morphological transformation was difficult to detect in an ordinary serum-supplemented medium. The hst-2 cDNA was cloned from the NIH3T3 transformant. Nucleotide sequence analysis of the cDNA indicates that the hst-2 gene encodes a 198 amino acid transforming protein containing a signal peptide with the characteristics of a heparin-binding growth factor. The coding sequence was almost identical to the published portion of the exon sequence of the FGF-6 gene, indicating that hst-2 is identical to FGF-6. The hst-2 cDNA fragment, when inserted into an expression vector, was able to transform NIH3T3 cells effectively, and the resulting transformant formed a well-vascularized tumor in nude mice, thus suggesting an angiogenic property similar to some other members of the family. RNA blot analysis revealed the expression of the hst-2 gene in human leukemia cell lines with platelet/megakaryocytic differentiation potential.