Periodic transcription of yeast histone genes has been demonstrated by DNA excess filter hybridization of in vivo pulse-labeled RNA isolated from synchronous cell cultures. Using strains carrying cell division cycle (cdc) mutations, we show that both activation and termination of transcription are determined by temporally separable (cell cycle) events. Activation of histone mRNA synthesis occurs late in G1, at a point prior to initiation of DNA replication. Cessation of histone mRNA synthesis, however, is dependent upon the entry of cells into S. These results suggest a simple model for the control of histone gene transcription in which changes in chromatin that must precede the initiation of DNA replication also bring about activation of histone mRNA synthesis. Cessation of synthesis would occur once this region had been replicated and the chromatin restored to its prereplicative state.