A comparison was made of responses to pharmacological agents between cell adhesion induced by an activator of Ca(2+)-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 Ca(2+)-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.