In a case-control study, we examined whether parental occupational exposures were related to neural tube defect (NTD)-affected pregnancies among Mexican Americans living along the Texas-Mexico border. Case women were 184 Mexican-American women with NTD-affected pregnancies; control women were 225 study-area residents who delivered normal babies during the same period as the case women. The women were interviewed in person about maternal and paternal occupations and work exposures during the periconceptional period. Compared with control women, case women were more likely to have had occupational exposures to solvents (odds ratio [OR], infinity; 95% confidence interval [CI], 2.4-infinity) and also were more likely to have worked in cleaning (OR 9.5; 95% CI, 1.1 to 82.2) or health care occupations (OR 3.0; 95% CI, 1.0 to 9.0) than control women. No compelling associations were found between paternal work exposures or occupations and NTDs in offspring in this population.