Acetaminophen, aspirin, ibuprofen, and amoxicillin are among the most commonly used drugs during pregnancy, but the safety of these medications with respect to birth defects is not established. Given the wide use of these drugs, even a small increase in the risk of birth defects may have considerable clinical and public health implications. We propose to evaluate the association between these drugs and 1) specific malformations previously hypothesized to be associated with each of them, and 2) specific malformations that occur most commonly in the general population. In addition, we propose to evaluate other commonly used medications by systematically screening each exposure in relation to the risk of specific malformations. These goals can be achieved at relatively modest cost by taking advantage of a large existing ongoing multicenter case-control surveillance program of birth defects in North America, the Slone Epidemiology Center Birth Defects Study (BDS). The BDS involves approximately 95 institutions in four metropolitan areas (Boston, Philadelphia, Toronto, and San Diego), and for over 25 years has interviewed over 20,000 mothers of malformed infants and over 4,000 mothers of non-malformed infants. The BDS identifies infants with a wide range of malformations within 5 months after birth at tertiary and birth hospitals, and within 6 months of delivery, study nurses interview mothers about demographic, reproductive, and medical factors; medication and vitamin use; cigarette smoking and alcohol consumption; and dietary intake. The study has discovered likely teratogenic effects that have subsequently been confirmed by others (e.g., salycilates in relation to gastroschisis). In the proposed analyses, we will estimate odds ratios and 95% confidence intervals using logistic regression, and results will be adjusted for potential confounders. Findings will test hypotheses about some drugs and provide leads for further research for others; both objectives seek to improve our understanding of risks associated with drugs commonly used by pregnant women.