Two different variants of the defective Friend spleen focus-forming virus (SFFV) have been isolated in the past. One of the strains (SFFV-P) induces polycythemia in susceptible mice and the other (SFFV-A) induces anemia. Although it was found that the envelope (env) gene of the different strains of SFFV was sufficient for induction of characteristic SFFV-a or SFFV-P disease, the molecular basis for the distinctive biological effects of the two variants is not known. We have constructed in vitro, env genes which are recombinants between the env genes of SFFV-A and SFFV-P. The env genes were constructed from molecularly cloned env genes of the two variants, using standard genetic engineering methods, and were tested for their biological activities both in vitro and in vivo. In these experiments ANA fragment of approximately 700bp at the 3 feet end of the SFFV env gene was found to encode the genetic differences between SFFV-A and SFFV-P.