To document changes of stress and illicit drug use among women from 4months prepregnancy to 6months postpartum. In a longitudinal study of drug use in family planning clinics, 121 women who became pregnant were matched with 202 women who did not become pregnant. Self-reported drug use, Cohen's Perceived Stress Scale, and open-ended stress questions were examined every 2months during the study period of time. Among drug-using pregnant women, drug use declined during 2nd and 3rd trimesters and increased immediately within 1 to 2months postpartum. Levels of perceived stress declined throughout pregnancy up to 2months postpartum, increased at 3 to 4months postpartum and then declined at 6months postpartum. In contrast, among nondrug-using pregnant women, stress remained stable until the 2nd trimester, increased from 3rd trimester to 1-2months postpartum, then declined continuously to 6months postpartum. For non-pregnant women, at the matched timeline, there was no clear pattern for changes of drug use and stress. Our study has illustrated a complex time course of changes of both perceived stress and drug use from prepregnancy through 6months postpartum. For drug-using pregnant women, pregnancy showed protective effect in reduction of both drug use and stress during pregnancy; and during postpartum, drug resumption peaked at 1-2months while stress peaked at 3-4months. If we can identify modifiable, pregnancy-related resiliency factors for both stress and drug use, we can begin to extend prevention efforts initiated during pregnancy into the postpartum period.