Isolated proximal renal tubules of rabbit reach a passive steady-state volume in isotonic medium after active transport is inhibited by ouabain or by inhibition of cellular metabolism or lack of metabolic substrates. If the tubules are then placed in a hypotonic NaCl medium they swell rapidly and then exhibit a volume regulatory decrease (VRD) similar to that seen when active transport is present. We have mathematically modeled these transient events by assuming that the basolateral cell membrane is permeated by pores having at least two distinct reflection coefficients with respect to sodium, potassium, and chloride. VRD depends on the difference of the values of the reflection coefficients of the pore types. As hydrostatic pressure is exerted by the stretching basement membrane, water and ions can be expelled from the cells across the lower reflection coefficient pores and cause VRD. When the hydrostatic pressure compliance is removed, the cells fail to volume decrease unless sufficient extracellular impermeant solute is present to provide an osmotic force for water and ion exit. We conclude that a heteroporous membrane may be an essential feature for cell volume regulation and maintenance.