We have previously demonstrated that the retinoblastoma gene family, Rb, p107 and p130, is differentially expressed during mouse embryogenesis. Here we show that this gene family is coordinately regulated in the mammary luminal epithelium. Expression of Rb, p107 and p130 in the epithelial compartment is low in nulliparous female mice and early stages of pregnancy but is induced at mid-pregnancy and peaks at lactation. During involution p107 expression is lost whereas expression pRb and p130 persist. The induction of this gene family at mid-pregnancy accompanies the expression of beta-casein. However, whereas beta-casein transcripts are confined to the lobuloalveolar compartment, the Rb gene family is expressed both in lobuloalveoli and ducts. The co-expression of the Rb family in the mammary gland may allow functional compensation among these family members. This in turn may explain the recent observations that loss of Rb alone in the mammary gland is inconsequential, whereas overexpression of cyclin D1 or SV40 large T antigen, which can abrogate all members of the pRb protein family, induces mammary gland carcinogenesis.