The apparent diffusion coefficient (ADC) and relaxation times of water were measured by magnetic resonance imaging (MRI) in the isolated turtle cerebellum during osmotic cell volume manipulation. The aim was to study effects of cell volume changes, a factor in ischemia and spreading depression, in isolation from considerations of blood flow and metabolism. Cerebella were superfused at 12-14 degrees C with solutions ranging from 50-200% normal osmolarity. Hypotonic solutions, which are known to cause cell swelling, led to reductions of ADC and increases of T(2), while hypertonic solutions had the opposite effect. This supports the concept that ADC varies with the extracellular space fraction and, combined with published data on extracellular ion diffusion, is consistent with fast or slow exchange models with effective diffusion coefficients that are approximately 1.7 times lower in intracellular than in extracellular space. Spin-spin relaxation can be affected by osmotic disturbance, though such changes are not seen in all pathologies that cause cell swelling.