The pattern of protein synthesis in the mouse egg shows several changes at fertilization and during first mitosis. Three groups of newly synthesized proteins, with molecular weights of about 30,000, 35,000, and 46,000, show variations in mobility on one- and two-dimensional gels that correlate with the cell cycle. Each group is composed of a polypeptide that is synthesized in unmodified form during interphase but is modified reversibly during meiosis or mitosis, by a process involving phosphorylation. Although these proteins cease to be synthesized during the second cell cycle, those made earlier persist and continue to show the same modifications during the next cell cycle. Like other eggs, fertilized mouse eggs show a requirement for protein synthesis in order to enter mitosis.