We examined the early phase of reovirus replication in interferon-treated L cells. No difference was detected in the adsorption of virus to cells, the rate and extent of conversion of parental virions to sub-viral particles (SVPs), and the protein and double-stranded RNA composition of the SVPs when comparing reovirus infection of the interferon-treated and control cells. Furthermore, when tested in vitro, SVPs isolated from interferon-treated cells (SVPINT) synthesized and methylated reo mRNAs at the same rate as SVPs isolated from control cells (SVPCON). However, the accumulated products of RNA synthesis promoted by SVPCON consisted mainly of full size reo mRNA molecules, whereas those whose synthesis was promoted by SVPINT consisted mainly of shorter products. These results indicate that premature termination of transcription and/or degradation of full size transcripts occurred in vitro with SVPINT. Other experiments revealed that a nuclease is associated with our SVPINT preparation.