The purpose of this study was to measure the effect of insulin-like growth factor-2 deficiency on the growth of the mouse conceptus. Initial observations on normal development in the 129J/Sv strain established that wet and dry weights were reduced by 35% when the insulin-like growth factor-2 gene was inactive. The DNA contents were reduced by only 15%. We exchanged the inner cell mass and trophectoderm between mouse blastocysts that had or lacked an active insulin-like growth factor-2 gene. At embryonic Day 16.5, lack of this gene's activity in the derivatives of either tissue decreased the fluid volumes of the exocelomic and amniotic cavities. The wet weights of the "fetal placentas," the yolk sacs, and the fetuses were also decreased. However, the tissue wet weight decrease could not be accounted for by the change in DNA content, indicating that cell-associated biomass had changed. The conclusions are 1) that insulin-like growth factor-2 levels regulate the composition of the fetus and extra-embryonic tissues and 2) that trophectoderm and inner cell mass derivatives cooperate to control extra-cellular fluid volume in the conceptus.