1. The c-H-ras was activated as a transforming gene in NIH/3T3 cells by its linkage to LTR sequences. The transformation, which was associated with high level of expression, could be transferred through several cycles of transfection. By molecularly cloning the transforming gene, we showed, unequivocally, that over-expression of the normal proto-oncogene was responsible for its transformation activity. 2. The normal protein-derived growth factor-2 (PDGF-2)/c-sis gene was activated as a transforming gene in NIH/3T3 cells. We constructed a series of recombinants in which a retroviral long terminal repeat (LTR) was linked to various regions of the human c-sis locus. The first construct, where LTR was linked to a region containing all the v-sis-related exons, lacked transforming activity, although sis-related transcripts were expressed. Insertion of a putative non-v-sis-related upstream exon between the LTR and the first v-sis-related exon resulted in a high-titered transforming activity equivalent to that of similar sarcoma virus (SSV) DNA. 3. To determine the biological activity of the human c-ras oncogene in mammalian cells, it was transferred within the genome of a retrovirus to cultured cells or inoculated into mice. Thus, the activated c-H-ras gene was inserted into the genome of Abelson murine leukemia virus (A-MuLV) or Moloney-MuLV. The defective viral particles were rescuable by superinfection with a helper amphotropic MuLV.