The env genes of Friend spleen focus-forming viruses (F-SFFV) have been implicated in the rapid pathogenicity of these agents. Two env-gene products are detected in SFFV-infected cells: the primary translation product, gp52, and a more highly processed form, gp65. In this communication we demonstrate that gp65 is the major end product of the SFFV env gene, and is efficiently secreted from both erythroleukemia cells and infected fibroblasts. Secretion was observed for the mature env-gene products of both polycythemia- and anemia-inducing strains of SFFV. These results suggest that one function of the point mutation near the 3' end of the env gene, which is invariant in the formation of SFFVs, is to allow secretion of gp65, and that secreted gp65 may be the factor mediating the leukemogenic activity of these viruses.