Our goal was to identify risk factors for substance use during pregnancy for primary care physicians so that we could assess a woman's risk of alcohol or illicit drug use. Participants were 2002 Medicaid-eligible pregnant women with < or =2 visits to prenatal care clinics in South Carolina and Washington State. Structured interviews were used to collect data. Logistic regressions and classification and regression trees identified predictors for pregnant women at high risk for substance use. Approximately 9% of the sample reported current use of either drugs or alcohol or both. Past use of alcohol or cigarettes, including during the month before pregnancy, most differentiated current drug or alcohol users from current nonusers. Our analysis suggests that primary care physicians can ask 3 questions in the context of a prenatal health evaluation to target women for referral to a full clinical assessment for drug and alcohol use.