PAUCKER, Cantell and Henle reported that crude mouse interferon preparations depressed multiplication of suspended L cells1. Since then evidence has accumulated indicating that interferon molecules which inhibit multiplication of virus also inhibit the growth of cells in culture2–9. Interferon was shown to suppress incorporation of 3H-thymidine into cellular DNA in various systems—for example, release from a double thymidine block in synchronised L929 cells10; activation of mouse spleen lymphocytes by phytohaemagglutinin (PHA) or allogeneic lymphocytes11; and in steady-state growth of cultured mouse leukaemia L 1210 cells12 in a chemostat. However, there has been no direct evidence to distinguish between the effect of interferon on the rate of initiation of DNA synthesis (entry into the S phase) and that on the rate of DNA synthesis in the S phase, and it is uncertain which step of the cell cycle is interfered by interferon. It is well known that most cells in cultures of confluent or serum starved mouse 3T3 stay in the early G1 or GO stage of the cell cycle, and an addition of serum to these quiescent cells stimulates their growth, leading to DNA synthesis and cell division13,14. We describe here a suppressive effect of interferon on the transition from the quiescent to the growing state in BALB/c 3T3 cells. The data indicate that interferon suppresses the initiation of DNA synthesis.