Insulin-like growth factor-II (IGF-II) expression has been implicated as a major determinant of fetal size during murine pregnancy. It remains unclear whether expression in the fetus, the placenta, or both is the overriding factor controlling growth. To gain further understanding of the placental contribution, we mapped IGF-II expression in the fetal vascular and trophoblastic portions of the late murine placenta (day 9.5–18.5). We found that, as in the fetus itself, vasculogenic mesenchyme, in this case derived from the allantois, was the strongest expressor of IGF-II. Trophoblast, on the other hand, while expressing somewhat less IGF-II, showed a dynamic pattern of IGF-II expression, which reflected its continuing differentiation during late pregnancy. Initially (days 9.5 and 12.5), the spongiotrophoblast, which is homologous to the cytotrophoblast columns and shell in early human pregnancy, strongly expressed IGF-II. Later, expression in the spongiotrophoblast was down-regulated as a new population, the 30-called glycogen cells, emerged within the spongiotrophoblast (day 12.5–15.5) and went on to invade the mesometrial decidua. Glycogen cells, which are homologous to human intermediate trophoblast, strongly expressed IGF-II. Trophoblast lining the area of maternalfetal exchange, the labyrinth, on the other hand, maintained a constitutive lower level of IGF-II expression throughout late pregnancy. © 1993 Wiley-Liss, Inc.