Our studies of the effect of purified mouse interferon on the replication of MuLV in clonal cell lines indicated that interferon treatment inhibits virus replication in acute, endogenous and persistant infections. The major interferon block is not due to the general inhibition of protein synthesis but occurs at the level of virus maturation and assembly. In acute infection and MSV induced transformation (without helper) interferon, a small and reversible block of the early viral function was also detected. In cells persistantly infected with MuLV noninfectious virions are produced containing, in addition to the major structural proteins, uncleaved and partially cleaved precursors of both env and gag gene product. It is our working hypothesis that the effect of interferon on MuLV assembly reflects and amplifies the anticellular effect of interferon (e.g., membrane effect) which is otherwise difficult to monitor on a biochemical level. Accordingly, we wish to examine and correlate 1) the molecular nature of MuLV inhibition and the anticellular activity of interferon, mainly its effect on mRNA population (cellular and viral) and its in vitro translatability effect on post-translational modification of proteins (e.g., glycosylation, phosphorylation) and rate of synthesis, and turnover of plasma membrane proteins and glycoproteins; 2) the effect of interferon on the physiological functions of plasma membrane and the membrane associated proteolytic activity. We believe that the new knowledge gained through these studies will bring about important commentaries on the effect of interferon on retrovirus replication and its anticellular and antitumor activity, as well as a more precise scientific rationale for the therapeutic use of interferon.