The effect of poly(I) . poly(C) on DNA and RNA synthesis induced in chicken embryo fibroblasts stimulated by calf serum from a quiescent to a growing state has been investigated. The results show that 1. poly(I) . poly(C) inhibits the induction of DNA synthesis in CEF stimulated by serum. 2. This inhibitory effect is dependent on the time between administration of poly(I) . poly(C) and stimulation, and is manifested at two discrete time intervals, at quiescent (Go) and late presynthetic (Gp) phases. 3. The 4-h incubation of quiescent cells with poly(I) . poly(C) before stimulation with calf serum inhibits and delays the onset of synthetic (S) phase, as manifested by the inhibition and retardation of induced DNA and RNA synthesis and by differences in the sedimentation profiles of total RNA synthesized at middle presynthetic phase of the stimulated cells.