The Friend spleen focus-forming virus (SFFV) a replication defective virus, induces erythroproliferative disease when injected as a pseudotype into susceptible mice. Some of the SFFV isolates will induce polycythemia (SFFV-P) while others will induce anemia (SFFV-A). The molecular basis for the distinctive biological effects of SFFV-P and SFFV-A in vivo is not known. Our approach to this problem was to clone molecularly, the genomes of SFFV-P and SFFV-A, to define the viral genes involved in the induction of disease by each variant, and compare the two genes on the molecular level. The genome of SFFV-P was molecularly cloned in our laboratory by D. Linemeyer. We have molecularly cloned the genome of SFFV-A from unintegrated proviral DNA and subsequently subcloned the env gene from the genomic clone. Both the genomic and env clones were biologically active and caused SFFV-A disease in mice. Since the env genes both of SFFV-A and SFFV-P were proven to be sufficient for induction of characteristic FVA or FVP disease we conclude that the biological differences between the two viruses map within the env gene of each virus.