The effects of high pressure (0.1-80 MPa) on cell adhesion were examined using Chinese hamster ovary cells. The cells detached by EDTA or trypsin were cultured for 4 h at atmospheric pressure. In each case, the rate of the adhesive cells was about 85%. Upon the addition of cycloheximide, such cell adhesion was almost completely inhibited in trypsin-treated cells but less affected in EDTA-treated cells. When the EDTA-detached cells were subjected to high pressures and cultured at atmospheric pressure, the cell adhesion was unaffected up to 40 MPa, but was suppressed significantly at higher pressures although the integrins were expressed on the plasma membranes. The suppressive effects induced by high pressure (80 MPa) were marked in trypsin-treated cells, in which the integrins were digested. Furthermore, actin stress fibers in spread cells disappeared due to cell rounding upon exposure to 80 MPa, and such rounded cells were partially detached from the substratum. These results suggest that the retardation of adhesion by high pressure in EDTA-detached cells may be due to the perturbed interactions between integrin and its associated proteins, whereas that of trypsin-detached cells is due to the delayed expression of integrins toward the membrane surface, in addition to the cause seen in the case of EDTA.