In some unknown manner, water uptake by brain cells (hyposmolality) promotes generalized seizure in humans and experimental animals, whereas cell dehydration (hyperosmolality) protects against it. We have replicated both scenarios in slices of hippocampus undergoing electrographic seizures. Surprisingly, a shift in osmolality does not change the excitability of individual neurons but rather, it alters the degree to which neurons interact. Hyposmolality enhances both excitatory synaptic transmission in neocortex and field (ephaptic) effects, the latter arising when cortical cells fire as a population. We propose that these increased excitatory interactions promote the synchrony that characterizes epileptiform activity.