Objective: Maternal drug use is known to have fetal central nervous system depressive effects as manifested by decreased biophysical profile scores. Drug effects on the amniotic fluid index (AFI), one variable of the biophysical profile, are not well documented. Our objective was to determine the effects of maternal drug use on the AFI. Study Design: Over an 18-month period from July 1997 to December 1998, consecutive cases of women with toxicology-proven drug use during pregnancy were identified. AFI values and the rate of polyhydramnios in substance users were compared with those observed at our institution in more than 6400 patients undergoing ultrasound testing during the same period as the cases. Results: Sixty-three toxicology-positive cases were identified. Although there was no significant difference between mean AFI values, the incidence of polyhydramnios (AFI >24 cm) was significantly higher in substance users (28.6%) than in control patients (3.9%) (P < .005). Conclusion: Maternal substance abuse is associated with a significantly higher incidence of polyhydramnios and should be considered a possible etiologic factor in women with apparent idiopathic polyhydramnios. (Am J Obstet Gynecol 2002;187:602-5.)