A comparison has been made of the effectiveness of periconceptional vitamin supplementation for the prevention of recurrence of neural tube defects (NTD) in south-east England and Northern Ireland. These areas represent the extremes of birth prevalence of NTD (low and high respectively) within the United Kingdom. Vitamin therapy resulted in a slightly less than two-fold reduction in the recurrence risk in south-east England and a greater than three-fold reduction in Northern Ireland, when compared with unsupplemented women at the same risk from the two areas. It is probable that one of the recurrences in each area did not involve the multifactorial form of NTD and, if these are excluded, then the reduction in recurrence risk with vitamin supplementation is 2.4 times in south-east England and 5.4 times in Northern Ireland. Either way, beneficial effects of supplementation are apparent in both areas but are more marked in the high prevalence area. The implications of this for the future are discussed. Two other important findings were that all but one of the recurrences of NTD with full supplementation occurred in male fetuses, and there was a higher than expected occurrence of isolated hydrocephalus in infants or fetuses following full supplementation.