Although neurologic dysfunction is a major cause of disability in patients with chronic renal failure, there is little knowledge of the underlying metabolic defect(s). We used a canine model to study the effects of chronic renal failure (CRF: 4 months after 1-7/8 nephrectomy, GFR 11 +/- 2 ml/min) on the composition and function of the nervous system. We also studied the effect of acute renal failure (ARF: 3.5 days after bilateral ureteral ligation) on peripheral nerve composition and function. In dogs with CRF for 4 months intracellular pH of brain and cerebro-spinal fluid (CSF) pH remained normal, despite metabolic acidemia. Osmotic equilibrium of the brain with plasma and CSF (and thus a normal water content) was maintained by almost equivalent increases in brain of urea and idiogenic osmoles (25 mmoles/kg H2O and 23 to 26 mOsm/kg H2O, respectively). Electrolyte concentration in brain tissue water did not change significantly. Calcium content was increased in cortical gray matter and hypothalamus of dogs with CRF, but was normal in the six other regions measured. Functional changes measured by the electroencephalogram were just as severe as those previously seen in dogs with ARF. The motor nerve conduction velocity (MNCV) was normal in dogs with ARF and did not change after up to 6 months of CRF.(ABSTRACT TRUNCATED AT 250 WORDS)