The purpose of this investigation was to examine the sex distribution of deaths from spina bifida in birth cohorts exposed and unexposed to severe periconceptional famine. For this purpose, we compared the risk of deaths from spina bifida between birth cohorts exposed and unexposed to the Dutch Hunger Winter of 1944-1946. In males, the relative risk of death from spina bifida was 2.62 [95% confidence interval (CI) = 1.14-6.01]. In females, the relative risk for spina bifida was 0.59 (95% CI = 0.14-2.37). The sex ratio (male:female) for deaths from spina bifida in the exposed birth cohort was 2.74; a female predominance was not seen in any other birth cohort. Deaths from anencephaly and other central nervous system disorders did not exhibit this male predominance in the exposed birth cohort. These findings indicate that severe periconceptional nutrient deficiency may have a greater effect on the occurrence of spina bifida in males vs females. Other potential explanations include sex-specific effects of prenatal famine on prenatal or postnatal survival rates of cases.