Concern with the frequency and patterning of the occurrence of midline neural-tube defects among contemporary human populations is widespread. These defects are, however, quite old and occur in unusually high numbers of prehistoric skeletons. A common explanation offered for such high incidence has been inbreeding among small, reproductively isolated populations. In a sample of 54 skeletons from the prehistoric south-western Indian site of Tijeras Pueblo in New Mexico, failure of neural-tube closure occurs in 10% of sacra recovered. While a more homogeneous genetic background and inbreeding may account for a portion of this elevated prevalence, the cause appears to lie with cultural-environmental factors. It is suggested that the aetiology of these conditions has become more complex in recent human history.