Maternal serum alpha-fetoprotein (AFP) screening of routine pregnancy is a valuable tool for the prenatal detection of neural tube defects (NTDs). Against our background experience with greater than 24,000 screened pregnancies, we have studied 411 pregnant insulin-dependent diabetic women. More than a tenfold increase (19.5/1,000) in the frequency of NTDs was observed in the offspring of these diabetic patients (p less than 0.000001). Serum AFP values were lower in diabetic than in nondiabetic women. Our data indicate that the normal standard of care for diabetic pregnancy should include serum AFP screening.