Tetrachloroethylene (PCE) is a solvent commonly used in dry cleaning, textile processing and metal degreasing. Because most of its use occurs in uncontrolled occupational settings, PCE is a common contaminant of U.S. public drinking water supplies and Superfund sites. While concerns about PCE are based mainly on its carcinogenicity and neurotoxicity, there is also mounting animal and human evidence that prenatal exposure to PCE increases the risk of birth defects. While these findings raise concerns for pregnant women, this body of literature is small and has weaknesses that hamper firm conclusions. Thus, we propose to conduct a population-based case-control study specifically designed to overcome the limitations of prior investigations. Building upon our prior Superfund research, the proposed study will test the hypothesis that prenatal exposure to PCE-contaminated drinking water is associated with oral clefts, neural tube, and cardiac defects. The study will identify 400 cases of oral clefts, 400 cases of neural tube defects, 400 cases of cardiac defects and 800 unaffected controls using live birth, fetal death, and medical records from Massachusetts and Rhode Island during the period 1969-1990. The source population includes approximately 279,269 live births and 1,954 stillbirths in 42 cities and towns whose public drinking water supplies were contaminated with PCE during this 22-year period. Case and control mothers will be sent a self-administered questionnaire to gather information on prenatal residential locations and demographic, behavioral and medical confounding variables. Data on environmental exposures that are potential confounders will be collected from historical records. Prenatal exposure to PCE-contaminated drinking water will be estimated using a leaching and transport exposure model developed and validated during our prior Superfund study. A quantitative bias analysis will be conducted to determine the impact of misclassification on the study results. Exposure assessment software and historical PCE contaminant levels will be shared with local water utilities and study findings will be communicated to local communities.