The effect of protein synthesis inhibitors on compaction of the 8-cell mouse embryo has been investigated. The effects observed depended upon the duration and time of drug application and on the features of compaction scored. Continuous application from the late 2-cell or early 4-cell stages allowed cell flattening and surface polarization to occur in most embryos and advanced development of these features in many of them. Cell coupling developed only when drug addition was delayed until the mid 4-cell stage, and cytoplasmic polarization developed only when drug addition was delayed until the late 4-cell stage. We suggest that control over the timing of compaction is achieved at a post-translational level via a global permissive change within the blastomeres of the embryo.