Pyridoxine is not completely innocuous. Large doses can cause a peripheral neuropathy despite renal excretion of this water-soluble vitamin. Renal failure patients are treated with pyridoxine to prevent a deficiency. The safety of pyridoxine treatment in the presence of renal dysfunction has not been studied. Our experiments on anephric rats show that the uremic state, in a mere 3 or 4 days, causes a 5- to 10-fold increase in susceptibility to pyridoxine-induced neuronopathy. These results suggest a need for caution in prescribing pyridoxine to uremic patients who will probably take the vitamin daily for many years.