Gastroschisis, an abdominal wall defect, most often occurs in infants of young mothers. To identify risk factors for gastroschisis, we conducted a case-control study in the population surveyed by the California Birth Defects Monitoring Program (CBDMP). From structured questionnaire data, we compared sociodemographic, reproductive, and lifestyle factors for 110 mothers of infants with gastroschisis with those for 220 age-matched mothers of normal infants. Univariate matched-pair analysis showed significant associations of gastroschisis with mother's education, yearly family income, marital status, a history of mother's mother smoking, mother's father's absence from home during the mother's youth, more than one elective abortion, a short interval between menarche and first pregnancy, siblings from different fathers, and use of either a recreational drug (either cocaine, amphetamine, marijuana, or LSD), alcohol, or tobacco during the trimester preceding pregnancy. For cocaine, amphetamine, and marijuana, use of more than one drug showed a stronger association than single drug use. The association was stronger if both parents used drugs. Although many variables were correlated, odds ratios (OR) were significant (95% confidence intervals) in multivariate conditional logistic analysis for: yearly family income < $10,000 [OR = 4.34 (1.54, 12.22)] or $10,000-$49,999 [OR = 3.93 (1.43, 10.80)]; mother's mother's smoking status not known [OR = 3.99 (1.66, 9.56)]; mother's father's absence from home during her youth [OR = 3.11 (1.14, 8.46)]; and drug use by mother [OR = 2.21 (1.21, 4.03)], father [OR = 1.66 (1.02, 2.69)], or both [OR = 3.05 (1.48, 6.28)]. The best predictive model explained 32% of the deviance. Young, socially disadvantaged women with a history of substance use were at highest risk for a child with a gastroschisis.