A comparison was made of responses to pharmacological agents between cell adhesion induced by an activator of Ca²⁺‐phospholipid‐dependent protein kinase (PKC) and physiological compaction in mouse embryos. An activator of PKC, 1‐oleoyl‐2‐acetyl‐sn‐glycerol (1,2‐OAG) induced the compaction‐like adhesion of cells in two‐cell embryos within 5–10 min and the adhesion lasted during the course of treatment for 1 h. W‐7 and W‐5 (calmodulin antagonists) and cytochalasin B and cytochalasin D (inhibitors of the polymerization of microfilaments) each completely interfered with the 1,2‐OAG–induced adhesion of cells. Two‐cell embryos having once shown evidence of cell adhesion in response to 1,2‐OAG were decompacted when they were transferred to a medium that contained 1,2‐OAG and any one of the agents described above. Colchicine and colcemid (inhibitors of the polymerization of microtubules) and tunicamycin (an inhibitor of N‐linked protein glycosylation) each had no effect on the 1,2‐OAG–induced adhesion of cells. In Ca²⁺ ‐free medium, treatment with 1,2‐OAG failed to induce any cell adhesion. These results are very similar to those reported for physiological compaction at the late eight‐cell stage. Thus, the compaction‐like adhesion of cells in mouse embryos at the two‐cell stage appears to be a calmodulin‐dependent process, requiring assembled microfilaments and extracellular Ca²⁺ ions but not microtubules or N‐linked glycoproteins as is the case for the physiological compaction. © 1993 Wiley‐Liss, Inc.