The adhesion of a cellular entity (liquid-filled microcapsule) to a flat glass substrate in response to an osmosis change is studied. A sensitive microscope visualization instrument has been developed to measure the cell-substrate contact area and inflated capsule volume. A theoretical model is developed to quantitatively correlate the adhesion energy to the contact area and osmotic inflation of cell volume. The results show that the contact area increased with increasing adhesion energy, while it shrank in dimension as cell inflation was enlarged. This observed phenomenon is consistent with the theoretical prediction. This work demonstrates the possibility of obtaining quantitative interfacial adhesion energy by using the present technique and represents the first step in extending this approach to study more complicated system such as cell-substrate interaction. (C) 2002 Elsevier Science B.V. All rights reserved.