Intrauterine growth retardation, a major source of fetal/infant morbidity and mortality, remains difficult to detect reliably before birth. In a previous study from our laboratory, determination of the presence of phosphatidylglycerol (PG) in amniotic fluid was found to be potentially useful for separating the growth-retarded fetus from the appropriately grown fetus of similar size. In the current study, this finding was confirmed and a clinical model for applying this method of detecting the small-for-gestational age (SGA) fetus was developed. Among 249 pregnancies in which ultrasound examination and amniocenteses were performed at or beyond 34 weeks' gestation and within a week of delivery, a fetal biparietal diameter of less than or equal to 87 mm and the presence of PG in amniotic fluid were found to be capable of detecting 80% of all SGA fetuses. Moreover, one half of the predictions of the birth of an SGA infant would have been correct. A positive screen with the use of this model was associated with a fifteen fold increase in risk for the birth of an SGA infant. These findings suggest a series of diagnostic steps to improve the antenatal detection of the growth-retarded fetus. (1) The clinician should assess risks and have a high index of suspicion. (2) When the at-risk pregnancy is thought to be at least 34 weeks, ultrasound examination may be helpful in confirming that the fetus is small. (3) Carefully amniocentesis, with the determination of PG, may then be useful in diagnosing intrauterine growth retardation.