Heterotrimeric G proteins of the G q class have been implicated in signaling pathways regulating cardiac growth under physiological and pathological conditions. Knockout mice carrying inactivating mutations in both of the widely expressed Gα q class genes, Gα q and Gα 11, demonstrate that at least two active alleles of these genes are required for extrauterine life. Mice carrying only one intact allele [Gα q (−/+); Gα 11 (−/−) or Gα q (−/−); Gα 11 (−/+)] died shortly after birth. These mutants showed a high incidence of cardiac malformation. In addition, Gα q (−/−); Gα 11 (−/+) newborns suffered from craniofacial defects. Mice lacking both Gα q and Gα 11 [Gα q (−/−); Gα 11 (−/−)] died at embryonic day 11 due to cardiomyocyte hypoplasia. These data demonstrate overlap in Gα q and Gα 11 gene functions and indicate that the G q class of G proteins plays a crucial role in cardiac growth and development.