The Smith-Lemli-Opitz syndrome (SLOS) is characterized by microcephaly, growth and mental retardation, unusual face, syndactyly of toes 2 and 3, and genital abnormalities. Since the original paper in 1964, this syndrome has been reported in over 70 patients. It is characterized by a specific combination of facial anomalies,(a. 0. ptosis, micrognathia, anteverted nares) and facultative genital abnormalities in males (hypospadias, cleft scrotum, cryptorchidism). Infrequent findings include cleft palate/uvula and postaxial polydactyly. Reported patients have had a wide range of developmental defects generally associated with severe mental retardation, but a few have been reported with borderline normal intelligence [Lowry and Yong, 19803. In general, multiple major structural anomalies are the exception rather than the rule in most SLOS patients surviving the neonatal period. However, among patients with SLOS, some have severe failure of masculinization (male pseudohermaphroditism) and multiple major structural abnormalities. Most of these infants die in the neonatal period. We report here on 19 similarly affected infants whose distinct findings include severe genital ambiguity in chromosomal males, postaxial hexadactyly, cleft palate, small tongue, eye anomalies, and cardiac defects. In addition, autopsy findings including unilateral renal agenesis, unilobated lungs, and large adrenals; intestinal aganglionosis and pancreatic islet cell hyperplasia have been noted with significant frequency in this group. We think that these patients either have a unique condition or represent the extreme end of the spectrum of the SLOS phenotype. Recognition of this more severe phenotype as a specific entity, which we choose to call SLOS-Type 11, is important as we have the impression that this phenotype may be more common than the condition as originally reported. We think that this condition is now frequently undiagnosed and usually is coded as a “multiple congenital anomaly syndrome of unknown etiology.”