It has been suggested that impairment of placental perfusion prior to delivery may manifest in early postnatal increase of creatinine values. We hypothesized that the smaller of a discordant set of twins would have a higher initial plasma creatinine value and decided to measure early plasma creatinine levels in discordant twins in order to evaluate whether this value may serve as an index of impaired placental perfusion. Plasma creatinine, urea nitrogen and blood hematocrit values were simultaneously measured in 35 sets of twins during the first day of life. The sets of twins were divided into 2 groups according to birth weight difference. Thus, 18 sets of discordant twins with birth weight difference greater than 15% comprised the GT group and 17 sets of twins with birth weight difference less than or equal to 15% comprised the LE group. The differences between the values obtained within each group were analyzed using the Wilcoxon Signed Rank test. In the GT group the mean plasma creatinine level of the smaller twins was significantly higher than the level of the larger ones (p = 0.03), but there was no statistically significant difference between values obtained in twins of the LE group. The mean plasma urea level was higher in the larger twins of both groups, however only the difference in the GT group was statistically significant (p = 0.01). The mean hematocrit of the smaller twins was higher in both groups, but only the difference in the LE group was statistically significant (p = 0.02). Generally, there was a negative correlation between gestational age and early creatinine values. These results apparently support the notion that prenatal exposure to impaired placental perfusion may compromise the creatinine clearance of the fetus and result in higher early creatinine values. Since the creatinine values in our growth-retarded twins were within the normal range, no distinguishing line for evidence of a uterine-placental compromise could be drawn. Whether a certain early plasma creatinine value is suggestive or indicative of an intra-uterine hypoxic-ischemic insult, should be determined by documented instances of severe fetal compromise prior to delivery.