A method is described for the measurement of tissue fluid osmolality in intact kidney slices using a vapor pressure osmometer (Wescor). The intact tissue slices were placed directly into the equilibration chamber of the instrument. A high degree of accuracy and reproducibility were obtained for both renal cortical and medullary tissue when care was taken to adhere to specific requirements for tissue slice geometry and size. The measurements proved to be technically easier than using the freezing point depression method, and better spatial resolution was obtained.