Reports in the literature have attributed a variety of structural defects in the newborn to prenatal cocaine exposure. Organ system involvement has included the brain, heart, skeleton, GI and GU tract. This sample was part of a longitudinal study of prenatally identified crack/cocaine users and controls and their offspring, designed to assess the teratogenic effect of cocaine exposure. Women were enrolled prospectively from a rural public health population and were matched on race, parity, prenatal risk, and SES (n=308). Drug use was determined through in-depth histories obtained after each trimester and urine screening for drug metabolites at study entry and delivery. All infants were examined within the first 96 hours of life by experienced examiners blinded to maternal history. Examiners used a modified checklist of 58 major anomalies, all defined in advance. Of the 301 living offspring at birth, 231 were included in the data analyses (119 control; 112 cocaine), excluding infants < 37 weeks gestation, those too sick to be examined in depth by 96 hours, and those missed due to scheduling errors. There were no significant differences between groups in the following measures: nipple width, ear length, palpebral fissure width, inner or outer canthal distance, interpupillary distance, philtrum, clitoral width or length or stretched penile length. The mean number of anomalies per child did not differ by group. The number of children within each group identified with an anomaly did not differ with over 75% of both groups having no identified major anomaly. No infant had more than 4 anomalies identified. The most commonly identified problem was a systolic heart murmur in 28 infants (11% cocaine; 13% control). Of interest was the identification of a single umbilical artery in 7 cocaine and 2 control infants. This study represents one of the first prospective, large-scale, blinded, systematic evaluation for congenital anomalies in cocaine-exposed infants and has failed to identify a consistent pattern of abnormalities. Specifically, in contrast to other reports, we did not find group differences in abnormalities of the skull, heart, skeleton, GI or GU tract.