Regulation of cell volume was one of the earliest evolutionary demands for life and remains a universal measure of cell metabolism. Since conventional methods to measure cell volume, such as microscopy, are complex and time-consuming, cell volume has not been used as the basis for cell-based screening. We have developed a microfabricated chip that can measure the volume of small numbers of cells in real time with unprecedented resolution. The method is applicable to adherent or suspended populations of cells and membrane-bound organelles. Our prototype device can detect volume changes in a monolayer of tissue-cultured astrocytes responding to anisotonic stimuli of <1mOsm. We determined the sensitivity to antibiotics of different E. coli strains in <10 min at 24 degrees C. This time can be reduced at higher temperatures enabling on-site clinical testing of infectious agents. Using the chip to screen natural products, we found a peptide in spider venom that inhibits eukaryotic volume regulation at approximately 100pM. The prototype chip made in silicon is inexpensive, reusable, and runs on low-voltage electrical power. The technology can be readily transferred to large arrays in plastic.