Interferon could be recovered from homologous cells to which it was applied but could not be recovered from heterologous cells. The amount of interferon that could be recovered from cells corresponded to the sensitivity of the cells to the antiviral activity of the interferon: mouse embryo fibroblasts, which were 5 to 10 times as sensitive as L-929 cells to interferon, bound 5 to 10 times more interferon than the latter, whereas Lpa cells, which were only one-third as sensitive as L-929 cells to interferon, bound only one-third as much as the latter. The concentration of cell-bound interferon was as much as 150 times the extracellular concentration of interferon applied to the cells. Interferon bound to cells at 4 C with the same efficiency as it did to cells at 37 C, and actinomycin D-treated cells bound interferon as well as normal cells. Even though the total amount of interferon bound to cells was as much as 30% of the amount of interferon applied to them, no loss of antiviral activity was detectable from the medium.