Expression of the ovalbumin gene in chicken oviduct explant cultures requires the presence of a somatomedin-like peptide hormone in addition to estrogen. Insulin, proinsulin and multiplication-stimulating activity (MSA) are equally active substitutes for this peptide hormone, and maximal induction requires about 0.5 micrograms/ml; fetal calf serum can partially substitute for these factors. The equipotency of insulin and proinsulin indicates that insulin receptors are not involved, and the activity of MSA suggests that the active receptor is specific for somatomedins. The permissive effect of the peptide factor occurs within 1-2 hr and is required for the initiation of estrogen-mediated transcription on the ovalbumin gene. In contrast, transcription from the conalbumin gene is fully induced by estrogen in the presence or absence of peptide factors or serum, despite the fact that these two egg white genes are both transcribed in the same cells in response to the same steroid hormones. We suggest that the interaction of a somatomedin with its membrane-bound receptor generates an intracellular signal that interacts specifically with the ovalbumin gene.