The clinical characteristics and neurologic outcome of 15 newborn infants with seizures due to hypocalcemia and hypomagnesemia have been studied with careful exclusion of those patients who had other possible etiologies for seizures. Associated diagnoses included severe congenital heart disease in 7 of 15 (47%) patients. Possible causes for this association with congenital heart disease include a forme fruste of DiGeorge syndrome, hypocalcemia and hypomagnesemia due to critical illness, and subtle embolic cerebral ischemia. In contrast with previous studies, no abnormalities of formula milk feeding were observed. Five patients (36%) died of causes unrelated to seizures. Follow-up in 8 of 9 patients who had no cerebral insults other than neonatal seizures at a mean age of 57.8 +/- 10.5 months found neurologic abnormalities in 2 (22%), both with an endocrine etiology for hypocalcemia. We conclude that infants with severe congenital heart disease should be investigated for hypocalcemia and hypomagnesemia. Previous observations of a universally favorable neurologic outcome in newborns with hypocalcemic or hypomagnesemic seizures may be valid for those who have a nutritional etiology for the metabolic disturbance but are less relevant to the current population in whom hypocalcemia or hypomagnesemia due to errors in formula milk feeding is seldom observed. In this group, neurologic prognosis may be more related to associated medical conditions.