Mouse embryos produced by the fertilization of eggs from (B6D2)F1 and CF-1 mice differ in their ability to complete the second cell cycle in the presence of alpha-amanitin. Essentially all embryos obtained from CF-1 mothers arrest at the two-cell stage when cultured from the late one-cell stage in alpha-amanitin at concentrations that prevent zygotic genome activation, while up to 15% of the embryos obtained from (B6D2)F1 mothers can progress to the three- to four-cell stage. This occurs even at alpha-amanitin concentrations that are fivefold greater than that required to prevent gene transcription. We propose that eggs of certain strains of mice may be endowed with greater supplies of macromolecules to support early development and that a percentage of these embryos can complete the second cell cycle in the absence of transcription. This difference may contribute to the strain-dependent differences in development in vitro.