The aim of the study was to document the frequency of neural tube defects (NTD) over a 20-year period in Cape Town and to determine the effects of race, gender, maternal age, parity and season of conception on the prevalence. Multiple sources of ascertainment were used, including all maternity hospital records, neurosurgical and spinal defects clinic data, as well as those from the Human Genetics Department and Fetal Abnormality Group. The prevalence rates for NTD fluctuated between 1.74 and 0.63 per 1,000 births, but showed no significant trends over the 20-year period. Prevalence rates were highest for the white population group of 2.56 per 1,000 births compared to 0.95 per 1,000 for blacks and 1.05 per 1,000 for those of mixed ancestry. The higher rates in the whites, who are of British and European extraction and belong to the more affluent section of the community, would suggest that the possible effects of nutrition and infection are overshadowed by genetic factors. There was a female preponderance for both spinal bifida (M:F ratio 0.89) and anencephaly (M:F ratio 0.67). The highest NTD rates were found at both ends of the maternal age range (< 20 years and > 35 years of age). The prevalence was highest at the extremes of birth order (1.65 and 1.58 for birth order 1 and > 7, respectively, and 0.56 and 0.45 for birth order 5 and 6, respectively). A seasonal variation occurred which differed from that reported for the Northern Hemisphere and may reflect local climatic conditions.