Maternal medication during the first trimester of pregnancy has been discussed as a risk factor for development of birth defects. The correlation between maternal drug use and major malformations was investigated in a population-based case-control study in Mainz. Over a period of 5 years (1990-1994), 20,248 livebirths, stillbirths, and abortions underwent physical and sonographic examination, and anamnestic data were collected. A total of 1,472 births with congenital anomalies (cases) and 9,682 births without major and minor malformations (controls) were analyzed. We distinguished between 30 different drug categories, which were divided into medication taken continuously (before and during pregnancy; CM) and acute medication (drugs given within the first 3 months of gravidity; AM). Statistically highly-significant results [CM: Odds Ratios (OR) 1.2, Confidence Intervals (CI) 1.1-1.4, were established for maternal drug use in correlation to birth defects. For the majority of combinations between drugs and specific malformations no teratogenic risks were found. However, statistically significant associations were recorded for antiallergics and heart anomalies (CM, AM) as well as musculoskeletal anomalies (AM); for bronchodilators and heart anomalies (CM, AM); for antiepileptics and anomalies of the internal urogenital system (CM), as well as cleft palatelcleft lips (AM); for thyroid hormones and anomalies of the nervous system (CM, P = 0.