The rate at which profound hyponatremia should be corrected is the focus of a recent clinical debate. We prospectively studied neurological outcomes with serial magnetic resonance imaging in 13 hyponatremic subjects with serum sodium concentrations of less than 115 mmol/L (mean initial serum sodium concentration, 103.7; range, 93-113 mmol/L). All subjects were corrected to mildly hyponatremic levels at 24 hours and ultimately underwent an increase in serum sodium concentration of 25 mmol/L without development of hypernatremia. Magnetic resonance imaging revealed the development of pontine lesions in 3 patients. The correction rate of hyponatremia over the first 24 hours was significantly faster in patients with pontine lesions (mean +/- SD, 1.25 +/- 0.4 mmol/(L . hr) versus 0.74 +/- 0.3 mmol/(L . hr); p less than 0.05). Initial sodium concentration was also significantly lower in the pontine lesion group (97.3 +/- 6.7 vs 105.6 +/- 5.2 mmol/L, p less than 0.05). We conclude that the correction rate of hyponatremia plays a significant role in the pathogenesis of pontine lesions in individuals with profound hyponatremia who undergo large increases in sodium concentration as a result of severe initial hyponatremia.