Many cell types regulate their volume in response to extracellular tonicity changes through a complex series of adaptive mechanisms. Several methods currently used to measure cell volume changes include: Coulter counters, fluorescent techniques, electronic impedance, and video microscopy. Although these methods are widely used and accepted, there are limitations associated with each technique. This paper describes a new method to measure changes in cell volume based on the principle that fluid flow within a rigid system is well determined. cos-7 cells were plated to line the inner lumen of a glass capillary and stimulated to swell or shrink by altering the osmolarity of the perfusing solution. The cell capillary was connected in series with a blank reference capillary, and differential pressure changes across each tube were monitored. The advantages of this method include: 1) continuous monitoring of changes in volume during rapid solution changes, 2) independence from cell morphology, 3) physiological conditions with cell surface contacts and cell-cell interactions, 4) no phototoxic effects like those associated with fluorescent methods, and 5) reporting from large populations of cells. The method was able to detect the previously demonstrated enhanced volume regulation of cells over-expressing the membrane phosphoprotein phospholemman, which has been implicated in osmolyte transport.