In a case-control study of gastroschisis, we evaluated the risks associated with mother's first-trimester use of medications and with hobby or occupational exposures for 110 cases and 220 controls without a birth defect. Mothers of cases and controls were age-matched. For hobby or occupational exposures, we found significantly elevated risks for high levels of solvents (odds ratio (OR) = 3.8; 95% confidence interval (CI) = 1.6-9.2) and for colorants (OR = 2.3; 95% CI = 1.3-4.0). For medications, we found significantly elevated risks for two strong cyclooxygenase inhibitors, aspirin (OR = 4.7; 95% CI = 1.2-18.1) and ibuprofen (OR = 4.0; 95% CI = 1.0-16.0), but not for acetaminophen, a weak cyclooxygenase inhibitor. Periconceptional exposure to X rays was also associated with gastroschisis (OR = 2.5; 95% CI = 1.2-5.5), but exposure to antibiotics, antinauseants, sulfonamides, or oral contraceptives was not. We also found elevated risks for two decongestants, pseudoephedrine (OR = 2.1; 95% CI = 0.8-5.5) and phenylpropanolamine (OR = 10.0; 95% CI = 1.2-85.6). For the group of all decongestants, including also oxymetazoline and ephedrine, the risk was significantly elevated (OR = 2.4; 95% CI = 1.0-5.4). Controlling in multivariate analyses for several demographic and pregnancy variables associated with gastroschisis in a previous analysis [Torfs et al. (1994) Teratology 50: 44-53] did not substantially change the level or direction of the associations. Most of these associations are for vasoactive substances, which supports a vascular hypothesis for the pathogenesis of gastroschisis.