To investigate the relationship between low unconjugated estriol (uE3) levels in the second trimester and adverse perinatal outcomes in pregnancies without increased risk for Down's syndrome, 1,096 women under 35 years of age underwent a mid-trimester AFP-hCG-uE3 screening test between January 1995 and June 1998. Multiple pregnancies, maternal diabetes, smoking and elevation of AFP and hCG levels more than 2.0 multiple of median (MoM) were excluded from our study population. The results were divided into a low-uE3 group with uE3 levels at or below 0.75 MoM and a normal uE3 group with uE3 levels above 0.75 MoM. The risk for adverse pregnancy outcome was compared between the two groups and the role of low uE3 as a predictor of adverse pregnancy outcome was determined. The data were assessed using χ² or Fisher exact test and then logistic regression was used for the final analysis. The odds ratio (OR) and corresponding 95% confidence intervals (CI) were also calculated. Unconjugated E3 levels at or below 0.75 MoM was significantly associated with fetal growth restriction after adjustment for maternal age, weight, sampling weeks, AFP and hCG levels (OR 0.413, 95% CI 0.174-0.900; P = 0.035). Low uE3 levels in the second-trimester could help in the detection of fetal growth restriction by a low risk group in Down's syndrome. Careful gestational dating and serial clinical and sonographic assessment of fetal growth may be required for the clinician to manage these parturients.