Newborn mice homozygous for a targeted disruption of insulin-like growth factor gene 1 (Igf-1) exhibit a growth deficiency similar in severity to that prevlously observed in viable Igf-2 null mutants (60% of normal birthweight). Depending on genetic background, some of the Igf·1(−/−) dwarfs die shortly after birth, while others survive and reach adulthood. In contrast, null mutants for the Igf1r gene die invariably at birth of respiratory fallure and exhibit a more severe growth deficiency (45% normal size). In addition to generalized organ hypoplasia in Igf1r(−/−) embryos, including the muscles, and developmental delays in ossification, deviations from normalcy were observed in the central nervous sysem and epidermis. Igf·1(−/−)/Igf1r(−/−) double mutants did not differ in phenotype from Igf1r(−/−) single mutants, while in Igf·2(−)/Igf1r(−/−) and Igf·1(−/−)/Igf·2(−) double mutants, which are phenotypically identical, the dwarfism was further exacerbated (30% normal size). The roles of the IGFs in mouse embryonic development, as revealed from the phenotypic differences between these mutants, are discussed.