Mouse oocytes were fertilized in vitro and the precise timing and sequence of morphological and molecular events occurring during the first cell cycle were investigated. The timing of development through the first cell cycle was found to be initiated by an event associated with sperm penetration rather than with germinal vesicle breakdown. DNA replication is initiated randomly in either pronucleus of a given egg, beginning approximately 11 h post insemination (hpi), and S phase lasting 6−7 h in both. Careful study of polypeptide synthetic profiles revealed three classes of changes in polypeptide synthesis during the first few hours of development: fertilization-independent, fertilization-accelerated, and fertilization-dependent. Pulse-chase experiments and in vitro translation of extracted mRNA showed that the changes in polypeptide synthetic profile result from differential mRNA activation, differential polypeptide turnover and post-translational modifications. These results support the notion that following ovulation, development is controlled at two levels. An endogenous (oocyte) programme, set in train by the terminal events of oocyte maturation, may regulate the ‘housekeeping’ functions of the egg, while sperm penetration activates a further endogenous (fertilization) programme, which may serve to initiate subsequent embryogenesis.