Whole-cell currents in mouse zygotes were measured using the patch-clamp technique in whole-cell mode. Upon exposure to hypotonic medium, patch-clamped zygotes increased in volume and developed a large swelling-activated current. The swelling-activated current was blocked by Cl- channel blockers, and the magnitude of the current and reversal potential were dependent on the Cl- gradient. Thus, the swelling-activated current had the properties of a current mediated by anion channels. However, in addition to being permeable to Cl- and I- (with I- having the greater permeability), there was also a significant swelling-activated conductance to aspartate and taurine, indicating that the swelling-activated channels in zygotes conduct not only inorganic anions but organic osmolytes as well. This swelling-activated anion and organic osmolyte pathway likely underlies the ability of zygotes to recover from an increase in volume, and it may function to regulate intracellular amino acid concentrations.