Studies performed in the CSV subline of mouse L-cells suggest that activated endogenous and/or exogenous viral infection might be the factor that modifies the cell surface and, in consequence, the sensitivity of the cell to the cell-growth inhibitory action of interferon. In contrast with the parental L-cells, the CSV subline obtained by prolonged passage of L-cells in the presence of interferon shows an altered electron microscopic morphology, absence of C type particles and a decreased agglutinability with Concanavalin A. It is resistant to the cell-growth inhibitory effect of interferon but retains the sensitivity toward its antiviral effect. However, the sensitivity of the CSV subline toward the cell-growth inhibitory effect of interferon increased significantly after treatment with 5-iododexyuridine, infection with the Harvey strain of mouse sarcoma virus and/or prolonged passages in vitro. In this respect, the CSV subline resembles the primary mouse embryonic cells. Since sensitivity of CSV cells increased also after treatment with cyclic 3'-5' adenosine monophosphate and/or prostaglandin E2, it is possible that the cell-growth inhibitory effect of interferon is mediated through the "second messenger" system.