Neural tube birth defects (NTDs) affect more than 4000 pregnancies in the US annually. The etiology of NTDs is believed to be multifactorial, but much remains unknown. We examined the pattern and magnitude of urban-rural variation in anencephaly, spina bifida without anencephaly, and encephalocele in Texas in relation with urban-rural residence for the period 1999-2003. There was no evidence that urban-rural residence was associated with changes in the rate of anencephaly or spina bifida without anencephaly in unadjusted or adjusted analyses. In contrast, rates of encephalocele were statistically significantly higher in areas classified as suburban or more rural compared to urban areas using four different urban-rural residence indicators.