The effect of adjustment of maternal serum alpha-fetoprotein levels for maternal weight was evaluated in 143 pregnancies associated with fetal open spina bifida. The cases were analyzed with gestational dates as initially assigned either by last menstrual period (73%) or by ultrasonography (27%). The weights of women with pregnancies affected by open spina bifida were found not to be different from unaffected pregnancies. Adjustment resulted in a net increase in detected cases at two commonly used cutoff points: 2.0 and 2.5 multiples of the median. At 2.0 multiples of the median, the detection rate increased from 80% to 84%, whereas at 2.5 multiples of the median the rate rose from 68% to 69%. Adjustment for maternal weight has previously been shown to reduce the false-positive rate in maternal serum alpha-fetoprotein screening for fetal open spina bifida by reducing variance in unaffected pregnancies; our data provide further support for consideration of maternal weight when interpreting material serum alpha-fetoprotein measurements.