To determine factors contributing to life-threatening brain herniation in patients treated for severe diabetic ketoacidosis, we analyzed history, laboratory data, rate and composition of fluid and insulin administration, and time to onset of brain herniation in nine new cases and 33 prior reports. The overall rate of fluid administration was inversely correlated with the time of onset of herniation (r = -0.32, p = 0.04). Only 4 of 40 cases occurred at fluid intakes less than or equal to 4.0 L/m2/day. During treatment, "calculated" serum sodium concentrations fell significantly and were less than 130 mEq/L in 33% of cases at the time of herniation. These data indicate that excessive secretion of vasopressin may exacerbate the brain edema, and that limitation of the rate of fluid administration may be prudent.