To determine the clinical significance of a high anion gap (more than 16 meq/liter), consecutive patients in whom electrolyte determinations were made in an emergency room and who had either a normal (8 to 16 meq/liter) (n = 571) or a high (n = 100) anion gap were contrasted. No differences were noted between the groups with regard to age or length of stay in the hospital, but in the group with a high anion gap, there was an increased severity and frequency of multiple electrolyte disorders, and higher general admission rates (66 percent with high anion gap versus 51 percent with normal anion gap, p less than 0.02), rates of admission to an intensive care unit (25 percent with high anion gap versus 14 percent with normal anion gap, p less than 0.03), and mortality within one week of admission (12 percent with high anion gap versus 0.5 percent with normal anion gap, p less than 0.001) as compared with the group with a normal anion gap. Notably, patients without severe electrolyte abnormalities and a high anion gap had higher admission rates and a 50-fold increased mortality rate as compared with the group without severe electrolyte disturbances and a normal anion gap. Thus, an elevated anion gap is associated with an increased severity of illness that is independent of concomitant severe electrolyte abnormalities. Patients with a normal or high anion gap that survived the first week of hospitalization were shown to have an extremely low risk for mortality.