In an attempt to develop model systems for understanding the mechanisms of type C virus-induced mouse leukemias, we have analyzed target cell specificities for transformation by different viruses. It has been possible to show that clonal strains of M-MuLV and R-MuLV induce tumors of T and B lymphoid cells, respectively. Since these viruses have similar genomic structures and code for related components, we reasoned that a genetic approach might make it feasible to localize the region of the viral genome responsible for target cell specificity. In efforts aimed at construction of molecular recombinants between Rauscher and Moloney leukemia virus genomes, we cloned the integrated proviral DNA of R-MuLV. Taking advantage of the common restriction sites that occur in the two viral genomes, we constructed several recombinants between the two proviral DNA molecules. These recombinant DNA molecules, when transfected into NIH/3T3 cells, yielded retroviruses that contained different regions of M-MuLV and R-MuLV DNA.