We report two patients who developed an acute, profound, and permanent sensory deficit after treatment with massive doses of parenteral pyridoxine. Aside from rapid onset, their clinical picture resembles that described in chronic pyridoxine neurotoxicity. It also is consonant with experimental models of acute pyridoxine intoxication and is probably secondary to a sensory ganglion neuronopathy. These patients also had transient autonomic dysfunction, mild weakness, nystagmus, lethargy, and respiratory depression. These previously undocumented features may be attributable to either the preservative used in the parenteral pyridoxine preparation or to the exceptionally high doses of pyridoxine these patients received.