In tertiary MEF undergoing cell cycle progression, autocrine interferon (IFN) is released and constitutive levels of 2',5'-oligoadenylate (2-5A) synthetase activity, low through the cell cycle, surge into a peak within S phase. Treatment of MEF with the autocrine IFN they produce elicits a 2-5A synthetase response from cells positioned in G0 but not from cells in G1 and from cells in S phase. Neutralization of the autocrine IFN by antibody shortens the length of G1 leaving unaltered the kinetics of progression through S and G2 and has no effect on the S phase-linked expression of 2-5A synthetase activity. The growth controlling effect of the autocrine IFN has been mapped to the second part of G1.