Abstract. During the course of preimplantation development, the cells of the mouse embryo undergo both a major subcellular reorganization (at the time of compaction) and, subsequently, a process of differentiation as the phenotypes of trophectoderm and inner cell mass cell types diverge. We have used antibodies specific for tyrosinated (Kilmartin, J. V., B. Wright, and C. Milstein. 1982. J. Cell Biol. 93:576-582) and acetylated (Piperno, G., and M. T. Fuller. 1985. J. Cell Biol. 101:2085-2094 ot-tubulin in immunofluorescence studies and found that subsets of microtubules can be distinguished within and between cells during the course of these events. Whereas all microtubules contained tyrosinated c~-tubulin, acetylated ot-tubulin was detected only in a subpopulation, located predominantly in the cell cortices. Striking differences developed between the distribution of the two populations during the course of development.Firstly, whereas the microtubule population as a whole tends to redistribute towards the apical domain of cells as they polarize during compaction (Houliston, E., S. J. Pickering, and B. Maro. 1987. J. Cell Biol. 104:1299-1308, the microtubules recognized by the antiacetylated oL-tubulin antibody became enriched in the basal part of the cell cortex. After asymmetric division of polarized cells to generate two distinct cell types (termed inside and outside cells) we found that, despite the relative abundance of microtubules in outside cells, acetylated microtubules accumulated preferentially in inside cells. Treatment with nocodazole demonstrated that within each cell type acetylated microtubules were the more stable ones; however, the difference in composition of the microtubule network between cell types was not accompanied by a greater stability of the microtubule network in inside cells.THOUGH the successive differentiative events of embryonic development depend upon the expression of a genetic program, cellular mechanisms exist that modulate that program and can direct the fate of a cell or of its progeny. During the preimplantation development of the mouse, it has been found that a series of such mechanisms are involved in the diversification of the first two cell types, inner cell mass and trophectoderm. The first is a dramatic cellular polarization which takes place during compaction at the eight-cell stage. At this time the blastomeres flatten upon each other and become polarized both at the surface and in the cytoplasm, such that by the end of the eight-cell stage the organization of the blastomeres has been changed from being radially symmetric to polarized, with the axis of polarity being oriented orthogonal to cell contacts. The second cellular mechanism is one of asymmetric cell division which operates on some of the polarized cells when they divide, and occurs as a consequence of their polarized organization. If the Evelyn Houliston's present address is