Russell-Silver syndrome (RSS) is a pattern of malformation characterized by intrauterine and postnatal growth retardation, limb asymmetry, triangular face, and hypospadias. We report on a patient, from a triplet pregnancy, who was one of identical male twins discordant for RSS. R.B. was a 710-g male born at 33 weeks of gestation, with hypospadias, chordee, and undescended testes. He had a normal 46,XY karyotype and no renal abnormalities. Female triplet A weighed 1,843 g, and male triplet B weighed 1,920 g. Both had normal physical findings and neonatal period. R.B. was first seen by us at age 6 7/12 years with short stature, triangular and asymmetric face, lower limb length discrepancy, and surgically repaired genital anomalies. Growth hormone testing results were normal. At age 8 7/12 years the brothers appeared physically identical except for size, with a height differential of 114.25 vs. 121.5 cm. Testing to establish biological zygosity was performed using VNTR (variable number tandem repeat) DNA probes YNH24 (D2S44), CMM101 (D14S13), EFD52 (D17S26), TBQ7 (D10S28), and 3'HVR (D16S85), PCR loci MCT118 (D1S80), and HLA-DQ alpha. These data indicate a > 99.99% probability of triplets B and C being monozygotic twins. While most occurrences of RSS are sporadic, familial cases suggesting autosomal dominance have been reported. Three other cases of probable monozygotic twins with RSS have been described. The significance of this confirmation of discordance in determining the cause of RSS is discussed.