The regulatory decrease in the volume of principal cells of collecting ducts to hypoosmotic shock has been investigated experimentally and using the mathematical modeling. A mathematical model of the response of collecting duct principal cells to hypotonic shock has been constructed on the basis of the experimental time course of changes in cell volume measured by the fluorescent dye Calcein. It was shown that the regulatory decrease in volume under hypotonic conditions occurs via a marked release of osmolytes and is accompanied by a decrease in water permeability of the cell membrane. The mathematical modeling of transmembrane transport processes allowed us to quantitatively estimate the changes in membrane water permeability, which decreased tenfold, from 2 x 10(-1) cm/s to 2 x 10(-2) cm/s. It was also shown that the effective regulatory decrease in the volume of collecting duct principal cells in hypotonic medium results from a significant increase in membrane permeability for K+, Cl-, and organic anions.