The distribution of water, electrolytes and non-electrolytes in various compartments of the central nervous system was analyzed in rats subjected to various stages of uremia. After bilateral nephrectomy for various periods of time ranging from 1 to 48 h, there is a progressive hyperkalemia, hyponatremia and metabolic acidosis. Although the cerebrospinal fluid (CSF) [K] progressively increases to a concentration of 6 mmol/l at 48 h post-nephrectomy, the ratio of CSF [K]/plasma [K] remains relatively constant throughout the duration of the uremic challenge; on the other hand, the concentration gradient for Na (CSF to plasma) markedly increases with progression of uremia. The steady rise in cellular [K] in both the choroid plexus and in at least one compartment of the cerebral cortex is presumably a reflection of stimulation of the Na-K pump caused by a build-up in [K] in the extracellular fluids of the brain. The blood-brain and blood-CSF barrier systems to both ¹⁴C-urea and ¹³¹I remain intact 24–48 h after nephrectomy; and there is not any evidence of cerebral edema at any stage of uremia. Thus, several lines of evidence indicate that the CSF-sink effect is maintained even in advanced uremia.