Maternal sources of transforming growth factor-\u03b21 (TGF-\u03b21) are shown here to contribute to the normal appearance and perinatal survival of TGF-\u03b21 null newborn mice. Labeled TGF-\u03b21 crossed the placenta and was recovered intact from various tissues after oral administration to mouse pups. TGF\u03b2-1 protein was also detected in cells recovered from breast milk. In immunohistochemical analyses, TGF-\u03b21 null embryos and null newborn pups born to TGF-\u03b21 heterozygotes stained positive for TGF-\u03b21, whereas those born to a null female were negative and had severe cardiac abnormalities. These results suggest an important role for maternal sources of TGF-\u03b21 during development and, more generally, provide evidence for maternal rescue of targeted gene disruption in the fetus.